Hsa_circ_0006988 Promotes Sorafenib Resistance of Hepatocellular Carcinoma by Modulating IGF1 Using miR-15a-5p

• Published in: Canadian Journal of Gastroenterology and Hepatology Vol. 2022; pp. 1206134 - 8
• Main Authors: Qiu, Rui, Zeng, Zhifeng
• Format: Journal Article
• Language: English; French
• Published: Egypt Hindawi 2022; Hindawi Limited
• Subjects: Angiogenesis; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Gene expression; Humans; Incorporation; Insulin-Like Growth Factor I - genetics; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; MicroRNAs; MicroRNAs - genetics; RNA, Circular - genetics; Sorafenib - pharmacology; Targeted cancer therapy; Variance analysis; United States > US; China
• ISSN: 2291-2789; 2291-2797
• DOI: 10.1155/2022/1206134

Background. Hepatocellular carcinoma (HCC) is the most frequently occurring cancer and contributes to the largest number of cancer-associated deaths worldwide. Recent evidence suggests that circular RNAs (circRNAs), which are critical for HCC etiology and metastasis, are distinctly modulated in HCC. Nevertheless, the underlying mechanism of circRNA-mediated sorafenib resistance (SOR) in HCC is yet to be determined. Methods. The hsa_circ_0006988, IGF1, and miR-15a-5p contents were quantified via ELISA and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Cell Counting Kit-8 (CCK-8) was used for the IC50 evaluation. Lastly, associations among hsa_circ_0006988, IGF1, and miR-15a-5p were validated through dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. Results. Herein, a new circRNA, hsa_circ_0006988, was identified, and its levels were markedly enhanced in SOR-resistant (SOR-R) HCC tissues. Functionally, hsa_circ_0006988 strongly suppressed SOR toxicity in vitro. Our examination of the signaling pathway revealed that hsa_circ_0006988 sequestered miR-15a-5p, a negative modulator of IGF1, thus suggesting that hsa_circ_0006988 deficiency diminished SOR resistance of HCC, and this action utilized the release of excess miR-15a-5p, which suppressed IGF1 levels. Moreover, miR-15a-5p overexpression reversed the hsa_circ_0006988-mediated SOR-R and enhanced IGF1 levels in HCC cells. Conclusion. Hsa_circ_0006988 partly promoted the SOR-R of HCC cells through miR-15a-5p sequestering and upregulation of IGF1 levels.