DigitalUM :: Browsing by Subject "Invasion"

Browsing by Subject "Invasion"

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Open Access
ACAT2 negatively modulated by FOXA2 suppresses ferroptosis to expedite the aggressive phenotypes of endometrial cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Xiao, Xin; Huang, Tingyun; Chen, Bin; Zhu, Jinshu; Xiao, Qingbang; Bao, Yuxin
Endometrial cancer (EC) remains a prevalent gynecological disease with a continuously rising incidence and fatality rate. Acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2) has been commonly perceived as a tumor promoter in multiple human malignancies. This study was conducted to specify the role and mechanism of ACAT2 in EC, which has not been covered. The expression and prognostic significance of ACAT2 in EC samples were respectively analyzed by the ENCORI and Kaplan-Meier plotter databases. RT-qPCR and western blot examined ACAT2 and forkhead box protein A2 (FOXA2) expression in EC cells. The CCK-8 method, colony formation, and EdU staining assays detected cell proliferation. The cell cycle was detected by flow cytometry analysis. Wound healing and Transwell assays, respectively, estimated cell migration and invasion. The thiobarbituric acid reactive species (TBARS) method and BODIPY 581/591 C11 probe detected lipid peroxidation levels. FerroOrange staining estimated intracellular iron level. Western blot examined the expression of epithelial-mesenchymal transition (EMT) and ferroptosis-associated proteins. The human TFDB database predicted the binding of FOXA2 with the ACAT2 promoter, which was substantiated by ChIP and luciferase reporter assays. As a result, ACAT2 expression was increased in EC tissues and cells and associated with poor survival outcomes in EC patients. ACAT2 deletion might hinder EC cell proliferation, migration, invasion, and EMT while stimulating cell cycle arrest. Moreover, ACAT2 silencing promoted the ferroptosis of EC cells. Also, FOXA2 inactivated the transcription of ACAT2 through binding with the ACAT2 promoter. FOXA2 interference could promote the proliferation, migration, invasion, EMT, cell cycle, and inhibit the ferroptosis of ACAT2-silenced EC cells, which was partially reversed by the ferroptosis activator erastin. Conclusively, ACAT2 transcriptionally inactivated by FOXA2 might contribute to the malignant progression of EC via the inhibition of ferroptosis.
Open Access
Cancer-associated fibroblast-secreted exosomes promote prostate cancer cell migration and invasion by the FGL1/SOX5 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Kong, Lingquan; Wang, Xing; Li, Yu; Zhang, Xiansheng
Exosomes secreted by cancer-associated fibroblasts (CAFs) play a critical role in cancer progression. This study aimed to explore the effects of CAF exosomes on prostate cancer (PC) cell metastasis. PC cells were treated with these exosomes, and their processes were evaluated using cell-counting kit-8 and Transwell assays. Exosome-regulated mRNAs were explored using quantitative real-time PCR. The relationship between FGL1 and SOX5 was analyzed using co-immunoprecipitation and fluorescence in situ hybridization (FISH) assays. The results of this study showed that exosomes derived from CAFs promoted PC cell viability, migration, and invasion. CAFs promoted PC cell viability and metastasis by releasing exosomes. Exosome treatment increased the levels of FGL1, which interacted with SOX5 and negatively regulated its expression. Rescue experiments demonstrated that CAF exosomes promoted the biological behaviors of PC cells by upregulating FGL1 and downregulating SOX5. Moreover, exosomes accelerated tumor growth by regulating the FGL1 level. In conclusion, CAF-derived exosomes promoted PC cell viability, migration, and invasion by elevating the FGL1/SOX5 axis, suggesting a novel strategy for the treatment of metastatic PC.
Open Access
Crumbs3: Expression and biological significance in normal and neoplastic tissues
(2026) Akane Kitta-Kunihiro; Chiemi Ikude; Eisaku Kondo; Hidekazu Iioka; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Cellular polarity plays a fundamental role in tissue organization and homeostasis, and its disruption is closely linked to tumorigenesis. Crumbs3 (CRB3), a conserved polarity protein, is essential for epithelial morphogenesis, tight-junction formation, and barrier function. This review summarizes current knowledge regarding CRB3 expression in normal and malignant human tissues and its dual roles in cancer progression. Systematic immunohistochemical analyses revealed strong CRB3 expression in non-neoplastic glandular epithelia of the gastrointestinal, hepato-pancreato-biliary, renal, and respiratory tracts, as well as in fetal tissues, suggesting its importance in organ development and maintenance. In neoplastic tissues, represented by colorectal adenocarcinoma and oral squamous cell carcinoma, CRB3 expression is preserved or even enhanced compared with normal tissues, which promotes tumor cell migration, triggering invasion/ metastasis as well as cellular proliferation through signaling pathways involving FGFR and RhoA activation. Conversely, previous studies reported that CRB3 functions as a tumor suppressor, based on findings that CRB3 expression induces loss of epithelial mesenchymal transition, whereas loss of CRB3 expression attenuates the integrity of tight junctions, resulting in significantly poorer prognosis in certain cancers. Current data thus suggest that the biological role of CRB3 in tumors is complex. Whether CRB3 acts as a tumor accelerator or suppressor may depend on the individual-specific, unique characteristics of tumor cells. Understanding these dual functions may contribute to the development of novel polarity-targeted therapeutic strategies for cancers of differing origin.
Open Access
Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-β signaling
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Chen, Dongdong Chen; Fan, Jiaxing; Li, Xianduo; Jiao, Zongshuai; Tang, Guanbao; Guo, Xuewen; Chen, Hao; Wang, Jianning; Men, Tongyi
Background. Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. Methods. The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. Results. The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-β signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. Conclusion. Our study reports the miR-485- 3p/TGFBR2/ TGF-β signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC.
Open Access
Elevated cathepsin K potentiates metastasis of epithelial ovarian cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Fan, Xiujie; Wang, Chongjuan; Song, Xianhui; Liu, Huaqing; Li, Xue; Zhang, Yuanfang
Cathepsin K, or CTSK, has been found to be involved in the peritoneal metastasis of ovarian carcinoma. However, the expression and clinicopathological significance of CTSK remains unknown in epithelial ovarian cancer (EOC). The aim of the present study was to investigate the expression of CTSK and its clinicopathological significance in EOC. TSK expression was evaluated using immunohistochemistry in EOC tissue microarray. The expression of CTSK in EOC was displayed to be markedly higher than that of adjacent normal control. In addition, CSTK expression was shown to be remarkably associated with metastases and inferior overall prognosis of EOC. In vitro, Knock-down of CTSD was exhibited to be able to suppress migration and invasion in EOC cell lines OV2008 but not proliferation in OV-2008. Together, our data showed that elevated CTSD in EOC can potentiate the metastasis of EOC cells, suggesting that targeting CTSD might be used as a novel therapeutic target for EOC.
Open Access
Fibroblast activation protein-alpha knockdown suppresses prostate cancer cell invasion and proliferation
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) An, Jiali; Hou, Dingkun; Wang, Lei; Wang, Lili; Yang, Yuanyuan; Wang, Haitao
Background. Prostate cancer is one of the most common malignant tumors of the male genitourinary system. Fibroblast activation protein alpha (FAP-α) overexpression has been shown to occur in a wide range of tumors. However, the specific mechanism of FAP-α in the development of prostate cancer has not been reported. Methods. In this study, real-time quantitative PCR (qRT-PCR) was used to detect the relative expression of FAP-α mRNA in prostate cancer cell lines (PC-3, LNCaP, and DU145) and human normal prostate epithelial cell line RWPE-1. Small interfering RNA (siRNA) targeting FAP-α and vectors expressing exogenous FAP-α were transfected to prostate cancer cells (LNCaP and DU145) to investigate the function of FAP-α. BALB/c nude mice were injected with DU145 cells which were transfected with NC-siRNA, FAP-αsiRNA-1, or FAP-α-siRNA-2. Results. Compared to adjacent normal tissues, FAPα protein and mRNA levels in prostate cancer tissues increased significantly (P<0.05). Compared to patients with high FAP-α mRNA levels, patients with low FAP-α mRNA levels had a significantly higher survival rate (χ2=5.050, log-rank P=0.025). Overexpression of FAP-α in LNCaP cells markedly inhibited cell apoptosis, and promoted cell invasion and proliferation. In contrast, knockdown of FAP-α expression in DU145 cells can significantly reduce invasion, proliferation, and promote apoptosis in prostate cancer. Immunofluorescence assay further indicated that down-regulation of FAP-α could suppress the nuclear translocation of β-catenin. An in vivo study found that compared with the NC-siRNA group, the tumor weight and tumor volume in the FAPα-siRNA-1 and FAP-α-siRNA-2 groups were significantly decreased. Conclusions. In conclusion, down-regulation of FAP-α can inhibit the invasion and proliferation of prostate cancer. Our study provides a theoretical basis for the targeted treatment of prostate cancer.
Open Access
Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Katagiri, Munetoshi; Karasawa, Hideaki; Takagi, Kiyoshi; Nakayama, Shun; Yabuuchi, Shinichi; Fujishima, Fumiyoshi; Naitoh, Takeshi; Watanabe, Mika; Suzuki, Takashi; Unno, Michiaki; Sasano, Hironobu
Background. It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. Patients and methods. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. Results. HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. Conclusion. These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients
Open Access
Infiltrated M2 tumour-associated macrophages in the stroma promote metastasis and poor survival in oesophageal squamous cell carcinoma
(2019) Zhou, Jian; Zheng, Shutao; Liu, Tao; Liu, Qing; Chen, Yumei; Ma, Rong; Tan, Doudou
Open Access
KIF22 promotes the proliferation and immune escape of endometrial cancer cells by activating the STAT3/PDL1 pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Chaohe Zhang; Chaoqun Wang; Biología Celular e Histología
Objective. Endometrial cancer (EC) is a common gynecologic malignancy with high morbidity and mortality. Kinesin Family member 22 (KIF22) is regarded as a critical oncogene, but its functions in EC progression remained elusive. Hence, this research elucidated the role of KIF22 in EC development and studied the possible mechanism. Methods. KIF22 expression in EC and the relationship with the overall survival of EC cases were determined by GEPIA and online K-M plotter. After transfection with sh-KIF22, cell viability and invasion were evaluated utilizing CCK-8 and Transwell assays. The content of IFN-γ, IL-2, and TNF-α was assessed utilizing an ELISA assay. The protein levels of p-STAT3, STAT3, and PD-L1 were examined using western blot. A xenograft tumor was constructed to assess tumor growth. Results. KIF22 was elevated in EC, with high KIF22 levels presenting poor overall survival. Additionally, silenced KIF22 restrained EC cell viability, invasion ability, and STAT3/PD-L1 pathway, enhanced the viability of CD8+ T cells, and elevated the levels of IFN-γ, IL-2, and TNF-α. Moreover, the rescue assay revealed that STAT3 overexpression counteracted the inhibitory effect of silenced KIF22 on EC cell proliferation, invasion and immune escape. Furthermore, silenced KIF22 repressed EC tumor growth and p-STAT3 and PD-L1 levels, and elevated the IFN-γ level in vivo. Conclusion. The findings demonstrated that KIF22 was elevated in EC and correlated with a poor prognosis. Silenced KIF22 repressed cell proliferation, invasion, and immune escape via suppressing the STAT3/PD-L1 pathway in EC.
Open Access
Knockdown of ADAMDEC1 inhibits the progression of glioma in vitro
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Liu, Xueliang; Huang, Hao; Li, Xuehan; Zheng, Xiaomei; Zhou, Chong; Xue, Bin; He, Jimin; Zhang, Ye; Liu, Liang
Background. Glioma is one of the most lethal malignant tumors all over the world. The prognosis of patients with high-grade glioma remains very poor. Therefore, it is urgent to find a novel strategy for the treatment of glioma. It has been reported that ADAMDEC1 could regulate the progression of multiple diseases, including cancers. However, the role of ADAMDEC1 during the tumorigenesis of glioma remains largely unknown. Methods, Gene expression of ADAMDEC1 in glioma tissues or in cells was detected by qRT-PCR. Western blot was performed to measure the protein expressions of p53, active caspase3, active caspase9, CDK2 and Cyclin A in glioma cells. Cell proliferation was detected by CCK-8 assay. Cell apoptosis or cycle was tested by flow cytometry. Transwell was used to test the invasion of glioma cells. Results. The expression of ADAMDEC1 in glioma tissues or cells was significantly upregulated. In addition, downregulation of ADAMDEC1 notably inhibited the proliferation and induced apoptosis of glioma cells through upregulation of active caspase 3 and active caspase 9. Besides, silencing of ADAMDEC1 obviously induced G1 arrest in glioma cells via modulation of cell cycle-related proteins. Finally, knockdown of ADAMDEC1 significantly inhibited the migration and invasion of glioma cells. In contrast, overexpression of ADAMDEC1 promoted cell proliferation, migration and invasion of glioma cells. Conclusion. Downregulation of ADAMDEC1 could significantly inhibit the tumorigenesis of glioma in vitro, which may serve as a novel target for the treatment of glioma
Open Access
LncRNA SNHG1 promotes nasopharyngeal carcinoma development via targeting miR-424-5p
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhou, Zheng; Chen, Yu
Objective. Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck. Distant metastasis and drug resistance are the main causes of cancer-related death. A better understanding of the molecular mechanisms that affect the progression of NPC would contribute to clinical treatment. This paper aims to investigate the effects of the long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on biological phenotypes of NPC cells and its related mechanisms. Methods. The expression of SNHG1 and miR-4245p in non-cancerous nasopharyngeal mucosa tissues and NPC tissues, as well as in normal nasopharyngeal epithelial cells and NPC cells was detected by qRT-PCR. HK1 and C666-1 cells were transfected with SNHG1 overexpression vector (OE-SNHG1), miR-424-5p mimic, SNHG1 knockdown vector (sh-SNHG1), or miR-424-5p inhibitor, followed by detection of transfection efficiency by qRT-PCR, cell viability by MTT, and invasive and migratory abilities by transwell invasion assay and cell scratch test. Moreover, the relationship between SNHG1 and miR-424-5p was detected by dual-luciferase reporter and RIP assays. Results. In NPC tissues and cells, SNHG1 was upregulated but miR-424-5p was downregulated. Transfection with OE-SNHG1 or miR-424-5p inhibitor promoted proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells; transfection of shSNHG1 or mi-miR-424-5p induced reverse trends. Mechanistically, SNHG1 negatively regulated miR-4245p expression, and transfection of miR-424-5p inhibitor counteracted the inhibitory effects of sh-SNHG1 on the proliferative, invasive, and migratory phenotypes of HK1 and C666-1 cells. Conclusion. LncRNA SNHG1 promoted proliferation, invasion and migration of NPC cells by repressing miR-424-5p expression.
Open Access
Matrix metalloproteinases in squamous cell carcinoma
(Murcia : F. Hernández, 2000) Johansson, N.; Kahari, V.M.
Controlled degradation of extracellular matrix (ECM) is essential in many physiological situations including developmental tissue remodeling, angiogenesis, tissue repair, and normal turnover of ECM. In addition, degradation of matrix components is an important feature of tumor growth, invasion, metastasis, and tumor-induced angiogenesis. Matrix metallo-proteinases (MMPs) are a family of zincdependent neutral endopeptidases, which are collectively capable of degrading essentially all ECM components. MMPs apparently play an important role in all the above mentioned aspects of tumor development. In addition, there is recent evidence that MMP activity is required for tumor cell survival. At present, several MMP inhibitors are in clinical trials of malignant tumors of different histogenetic origin. In this review we discuss the current view on the role of MMPs and their inhibitors in development and invasion of squamous cell carcinomas, as a basis for prognostication and therapeutic intervention in these tumors.
Open Access
MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Dong, Liangliang; Jiang, Hanliang; Qiu, Ting; Xu, Yiming; Chen, Enguo; Huang, Aihua; Ying, Kejing
We herein discuss the impacts of miR-101-3p on the tumorigenesis-related cell behaviors in lung squamous cell carcinoma (LUSC) by repressing KPNA2. TCGA database was utilized to measure miR101-3p and KPNA2 levels in LUSC tissues and cells. The interaction of miR-101-3p and KPNA2-3’UTR was determined by dual luciferase assay. Western blot evaluated the protein level of KPNA2. MiR-101-3p was under-expressed in LUSC cells while KPNA2 was overexpressed. Western blot confirmed the impact of KPNA2 expression on cancer cell progression. The negative regulatory impact of miR-101-3p on KPNA2 was also verified. In vitro cell function assays revealed the suppressing effect of high miR-101-3p expression on cell invasion, migration and viability, as well as its promoting effect on apoptosis. Up-regulated miR-101-3p weakened the promoting effect of overexpressed KPNA2 on LUSC malignant progression. To conclude, miR-101-3p repressed viability, invasion, and migration, and facilitated cell apoptosis in LUSC by suppressing KPNA2.
Open Access
MiR-195-5p suppresses gastric adenocarcinoma cell progression via targeting OTX1
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Hu, Sizhe; Zhou, Huanting; Zhao, Xiaokang; Qian, Feng; Jin, Cancan
Gastric adenocarcinoma (GAC) caused by malignant transformation of gastric adenocytes is a malignancy with high incidence. MiR-195-5p modulates a variety of cancers. One of its target genes, orthodenticle homeobox 1 (OTX1), is believed to be a key modulator of tumor progression. We aim to analyze the mechanism of miR-195-5p and OTX1 in GAC. MiR195-5p and OTX1 mRNA levels in GAC cells were tested via qRT-PCR. OTX1 protein and EMT-related protein levels were examined through western blot. Several cell functional assays were designed to measure changes in cell malignant behaviors. Dual luciferase assay verified the targeting relation of miR-195-5p and OTX1. These experimental results showed significantly low miR-195-5p expression and significantly high OTX1 expression in GAC cells. Enforced miR-195-5p level repressed cell malignant progression and accelerated cell apoptosis in GAC. Increased OTX1 weakened the above-mentioned effect caused by overexpressing miR-195-5p. Thus, miR-195-5p restrained migration, proliferation, invasion and epithelial-mesenchymal transition process of GAC cells, and promoted cell apoptosis through regulating OTX1. A new insight is provided for searching for biomarkers or therapeutic targets of GAC.
Open Access
MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Zhang, Chunying; Chang, Qing; Hu, Yaojie; Chang, Wang; Guo, Xin; Fu, Liru; Tang, Guoshuai; Chen, Chunyou
Objective. An increasing number of studies indicate that miR-222-3p is upregulated in various cancers and can regulate tumor progression. This study aimed to explore the regulatory mechanism of miR-222- 3p in papillary thyroid carcinoma (PTC). Methods. TCGA database was used to dig differentially expressed miRNAs and mRNAs in PTC tissue. Relevant references were searched to determine target miRNA. StarBase, TargetScan and miRDB were applied to predict mRNAs that had binding sites with the target miRNA. Then, the mRNAs were intersected with differentially downregulated mRNAs in TCGA to determine the target mRNA. qRT-PCR was exerted to evaluate gene expression of miR-222-3p and SLC4A4 in PTC. Western blot was performed out to evaluate the protein expression of SLC4A4 in PTC cells. CCK-8, wound healing assay and cell invasion assay were undertaken to observe the proliferative, migratory, and invasive abilities of PTC cells. Dual-luciferase assay was employed to test the binding relationship between miR222-3p and SLC4A4. Results. MiR-222-3p was highly expressed in PTC while SLC4A4 was lowly expressed. Moreover, miR222-3p was able to promote the proliferation, invasion, and migration of PTC cells. SLC4A4 was able to reverse these promotive effects of miR-222-3p. Conclusion. MiR-222-3p can promote the proliferation, migration and invasion of PTC cells through targeting SLC4A4. MiR-222-3p is expected to be a molecular therapeutic target for PTC patients.
Open Access
MiR-29c-3p represses gastric cancer development via modulating MEST
(2023) Li, Honghai; Lv, Jieqing; Wang, Jindao; Wang, Haifeng; Luo, Liang
Gastric cancer (GC) triggers a great number of deaths worldwide. Although great efforts have been made in treating this cancer, GC patients’ survival rate remains unsatisfactory. An increasing amount of evidence indicates that miR-29c-3p inhibits cancer progression. However, the mechanism of miR-29c-3p in GC remains to be fully defined. Hence, this work aimed to analyze the underlying mechanism of miR-29c-3p in GC. Outcomes showed marked downregulation of miR29c-3p in GC tissue and cell lines. Functional experiments exhibited that miR-29c-3p repressed GC cell malignant behaviors. Moreover, bioinformatics analysis and dual-luciferase reporter gene detection indicated that MEST was targeted by miR-29c-3p. Rescue assay further proved that MEST participated in functions of miR-29c-3p in GC. To sum up, miR-29c3p/MEST signaling pathway suppressed formation of malignant phenotypes of GC, and targeting the signaling pathway may be a new method for treating GC.
Open Access
MiR-486-5p specifically suppresses SAPCD2 expression, which attenuates the aggressive phenotypes of lung adenocarcinoma cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Wei, Desheng
. Background. MiR-486-5p expression is restrained in lung adenocarcinoma (LUAD). However, much less has been understood on its role in LUAD. We aimed to explore the biofunctions of miR-486-5p in LUAD. Methods. A differential expression analysis based on The Cancer Genome Atlas-LUAD dataset was done to screen the differently expressed miRNAs and mRNAs. MiR-486-5p and SAPCD2 mRNA expression was analyzed by qRT-PCR, and protein level of SAPCD2 was assayed by western blot. Upregulation and downregulation of miR-486-5p or SAPCD2 were achieved by cell transfection. For cell function assays, the proliferation of cancer cells was examined by MTT assay. Cell apoptosis was assessed by flow cytometry and microscopy. Transwell assay was applied to evaluate cell migration and invasion. A dual-luciferase detection was employed to determine the miRNA-mRNA targeting relationship. Results. MiR-486-5p expression was notably reduced in LUAD tissue and cell lines. Upregulating miR-486-5p restrained the anti-apoptotic and proliferative abilities, as well as cell migratory and invasive phenotypes in LUAD cells. SAPCD2 was determined as one target of miR-486-5p. Also, SAPCD2 forced expression was able to attenuate the inhibitory impacts of miR-486-5p on the malignant phenotypes of LUAD cells. Conclusion. MiR-486-5p suppressed cell malignant progression in LUAD by targeting SAPCD2, suggesting that the two may be targets for LUAD treatment.
Open Access
Nephronectin is a prognostic biomarker and promotes gastric cancer cell proliferation, migration and invasion
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Mei, Di; Zhao, Bochao; Zhang, Jiale; Xu, Huimian; Huang, Baojun
Gastric cancer (GC) is a malignant disease with high incidence and mortality rates worldwide. Nephronectin (NPNT) was found to be dysregulated in some kinds of cancer. The goal of our study was to explore the expression profile of NPNT based on large numbers of GC samples with detailed clinico- pathological and prognostic data from our institution and the data from a public database. A total of 117 GC samples and 73 corresponding non-tumorous adjacent tissues (NATs) were obtained from GC patients and used to detect expression of NPNT through immunohisto- chemistry. Western blot and qRT-PCR were performed to examine expression of NPNT in GC cell lines. Our results found that the positive expression ratio of NPNT in GC tissues is significantly higher than that in NATs (p<0.001). Chi-squared analysis results showed positive expression ratio of NPNT was significantly associated with depth of tumor invasion (p=0.049) and TNM stage (p=0.017). Kaplan-Meier survival and cox analysis results showed that patients with positive NPNT protein expression tend to have poorer prognosis than those with negative NPNT expression (p=0.0032) and NPNT expression was independent prognostic factor. High expression level was seen in GC cell lines. Furthermore, through a series of cancer cell proliferation, invasion and migration associated experiments, we found that NPNT could evidently promote GC cell proliferation, invasion and migration, as well as epithelial-mesenthymal transition. In summary, NPNT was evidently overexpressed in GC and had an oncogenic role. In the future, NPNT could serve as a promising therapeutic target for treating GC patients.
Open Access
POM121 is a novel marker for predicting the prognosis of laryngeal cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Zhao, Ruihua; Tang, Genxiong; Wang, Tengqi; Zhang, Lingli; Wang, Wei; Zhao, Qiangfang; Kun Zhao, Kun Zhao
The nuclear pore membrane protein 121 (POM121) is an important member of the nuclear pore complex which regulates nucleocytoplasmic transport, but little is known about the role of POM121 in laryngeal cancer. In this study, quantitative real-time polymerase chain reaction and immunohistochemistry were performed to detect POM121 expression in laryngeal tissues. The associations between POM121 and clinicopathological characteristics and overall survival in laryngocarcinoma patients were also analyzed. The mechanism of POM121 was preliminarily explored through gene set enrichment analysis (GSEA). mRNA and protein expression of POM121 in laryngocarcinoma tissues were higher than those in nontumor tissues. High POM121 expression was positively correlated with poor differentiation (χ²=42.391, P<0.001), advanced distant metastases (χ²=20.346, P<0.001) and TNM stage (χ²=23.436, P<0.001). Laryngocarcinoma patients with high POM121 level tended to have poor overall survival. GSEA confirmed that the mechanism of POM121 in laryngeal cancer may relate to sphingolipid metabolism, lysosome, fatty acid metabolism, ribosome, nucleotide excision repair and the PPAR signaling pathway. Overall, POM121 expression might be a prognostic biomarker in laryngeal cancer, and POM121 has the potential to present as a therapeutic target for laryngocarcinoma patients
Open Access
SIRT4 is associated with microvascular infiltration, immune cell infiltration, and epithelial mesenchymal transition in hepatocellular carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Li, Juan; Zhao, Ming; Fan, Weiwei; Na, Na; Chen, Hui; Liang, Ming; Tai, Sheng; Yu, Shan
Aims. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In the present study, we evaluated SIRT4 expression levels in HCC specimens and investigated the relationships between SIRT4 expression levels, clinicopathological factors, and microvascular infiltration (MVI) in HCC. Methods. The expression levels of SIRT4 in 108 HCC specimens were examined by immunohisto-chemical staining. MVI in HCC specimens was divided into three subtypes: M0, M1, and M2. Comprehensive bioinformatics analysis was carried out to demonstrate SIRT4’s biological functions and expression-related prognostic value. Results. The diffuse cytoplasmic expression pattern of SIRT4 was observed in all adjacent nonneoplastic liver tissues. The levels of SIRT4 were higher in HCC than in any other type of cancer and normal tissues. In addition, the expression levels of SIRT4 were significantly decreased in HCC tissues when MVI was M1 or M2 (P=0.003) but were not related to the overall clinical outcome. To explain MVI regulated by SIRT4, we also found that SIRT4 expression correlated with epithelial-mesenchymal transition (EMT) markers and CD4+ T/NK cells and downregulated cancer-associated fibroblast cells. Also, there was a significant relationship between MVI and degree of cell differentiation (P=0.003), tumor size (P<0.001), alpha fetoprotein (AFP) (P=0.001), alanine aminotransferase (ALT) (P=0.024), and γ-glutamyl transferase (γ-GT) (P=0.024). However, SIRT4 was not an independent prognostic marker of HCC. Conclusions. Our results demonstrated an association between SIRT4 expression levels, MVI, immune cell infiltration, and potential biological functions, including EMT in the progression of HCC.