Publication:
Hsa_circ_0088036 promotes tumorigenesis and chemotherapy resistance in hepatocellular carcinoma via the miR-140-3p/KIF2A axis

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Wang-40-1239-1251-2025.pdf(8.07 MB)
Date
2025
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Authors
Wang, Zhong ; Wang, Lei ; Yin, Guoqing ; Li, Heng ; Zhang, Rong ; Feng, Yuan ; Chang, Wen
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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Biología Celular e Histología
DOI
https://doi.org/10.14670/HH-18-849
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info:eu-repo/semantics/article
Description
Abstract
Background. Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. There are limited treatment options, particularly for chemotherapy-resistant HCC patients. Circular RNA hsa_circ_0088036 was associated with the development of bladder cancer and non-small cell lung cancer. However, whether it might be a potential therapeutic target for HCC remains elusive. Methods. Hsa_circ_0088036 expression was detected in HCC tumor tissues and cell lines using real-time PCR. The influences of hsa_circ_0088036 on proliferation and invasion as well as chemotherapy sensitivity in HCC cells were investigated by gain- and loss-of-function analyses. Associations among hsa_circ_0088036, miR-140-3p, and KIF2A were validated by real-time PCR, miRNA pull-down assay, dual-luciferase reporter assay, and western blot. Furthermore, a rescue experiment using KIF2A overexpression was performed to evaluate the regulatory mechanism of hsa_circ_0088036 in HCC cells. Additionally, the effect and mechanism of hsa_circ_0088036 were confirmed in a xenograft mouse model. Results. Hsa_circ_0088036 was highly expressed in HCC tissues and cells, with even higher expression in oxaliplatin-resistant cells. This expression was positively correlated with tumor size and TNM stage of the patients. Overexpression of hsa_circ_0088036 promoted the proliferation and invasion of HCC cells, while silencing mediated the opposite effects. Meanwhile, knockdown of hsa_circ_0088036 enhanced chemo-therapy sensitivity, including oxaliplatin, doxorubicin, and sorafenib, in HCC cells. Furthermore, hsa_circ_ 0088036 silencing inhibited tumor growth and increased oxaliplatin sensitivity in vivo. Mechanically, hsa_circ_0088036 functioned via the miR-140-3p/KIF2A axis with the activation of PI3K/Akt and Notch signaling pathways. Conclusions. Hsa_circ_0088036 promoted HCC tumorigenesis and chemotherapy resistance by activating the PI3K/Akt and Notch pathways through regulating miR-140-3p/KIF2A signaling. Thus, hsa_circ_0088036 may be a potential therapeutic target in chemotherapy-resistant HC
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Hsa circ 0088036 , Hepatocellular carcinoma , Oxaliplatin resistance , miR 140 3p , KIF2A
Citation
Histology and Histopathology Vol. 40, nº08 (2025)
URI
http://hdl.handle.net/10201/157352
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Histology and histopathology Vol.40, nº8 (2025)
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