circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression
Mingshuang Lai,
Meiliang Liu,
Deyuan Li,
Ruirui Zhang,
Lijun Wang,
Xiaofei Li,
Sixian Chen,
Siqian Wu,
Suyang Xiao,
Liling Wei,
Xiaogang Wang,
Aruo Nan,
Xiaoyun Zeng
Affiliations
Mingshuang Lai
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Meiliang Liu
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Deyuan Li
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Ruirui Zhang
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Lijun Wang
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Xiaofei Li
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Sixian Chen
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Siqian Wu
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Suyang Xiao
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Liling Wei
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Xiaogang Wang
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China
Aruo Nan
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China; Corresponding author
Xiaoyun Zeng
School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China; Corresponding author
Summary: Many circular RNAs (circRNAs) have been identified to be associated with hepatocellular carcinoma (HCC) progression. We aim to explore the diagnostic potential, functions, and mechanism of circELMOD3 in HCC. Differentially expressed circRNAs in HCC and its paired adjacent tissues were identified by RNA sequencing. circELMOD3 was downregulated in HCC tissues and was related to clinicopathological characteristics of HCC patients. Additionally, plasma circELMOD3 was shown to be a highly sensitive and non-invasive biomarker to distinguish HCC from healthy controls. Functional assays showed that circELMOD3 inhibited proliferation and induced apoptosis of HCC cells both in vitro and in vivo. Mechanistically, RNA antisense purification (RAP) and luciferase reporter assays verified that circELMOD3 functioned as a sponge for miR-6864-5p leading to increased expression of its target gene TRIM13. Interestingly, RNA stability test demonstrated that circELMOD3 overexpression led to enhanced stability of its directly bound TRIM13 mRNA, which in turn co-activated the p53 signaling pathway.