Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis

Ning Lyu; Yan Zeng; Yanan Kong; Qifeng Chen; Haijing Deng; Shunling Ou; Yanfang Bai; Hailin Tang; Xiaolan Wang; Ming Zhao

doi:10.21037/atm-21-997

Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis

Ann Transl Med. 2021 Apr;9(8):675. doi: 10.21037/atm-21-997.

Authors

Affiliations

¹ Department of Minimally Invasive Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangzhou, China.
² Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangzhou, China.
³ Reproductive Center of Medicine, The First Affiliated Hospital of University of South China, Hengyang, China.

Abstract

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs that have been demonstrated to play important roles in tumorigenesis. However, how circRNAs regulate the progression of hepatocellular cancer (HCC) remains unclear.

Methods: In the present study, circRNA microarray analyses were performed with HCC tissues to identify circRNAs that are differentially expressed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was conducted on HCC cell lines and tissues, and circ0097009 was found to be significantly upregulated. The functions of circ0097009 in HCC were investigated by a series of experiments, including cell proliferation, invasion, and mouse xenograft assays. Additionally, luciferase assays and RNA immunoprecipitation (RIP) assays were used to explore the interactions of circ0097009, microRNA-1261 (miR-1261), and solute carrier family 7 member 11 (SLC7A11) in HCC.

Results: Microarray analysis and qRT-PCR verified that circRNA, circ0097009, was significantly upregulated in HCC tissues and cell lines. Knockdown of circ0097009 inhibited the proliferation and invasion of HCC cells. Luciferase reporter assays showed that circ0097009 and SLC7A11 directly bound to miR-1261. Subsequent experiments showed that circ0097009 and SLC7A11 reciprocally regulated their expression via miR-1261 sponging by circ0097009.

Conclusions: Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in HCC. Circ0097009 may be used as a diagnostic biomarker for HCC and as a potential target for HCC therapy.

Keywords: Circular RNAs; SLC7A11; competitive endogenous RNAs; hepatocellular carcinoma; miR-1261.