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Long noncoding RNA semaphorin 6A-antisense RNA 1 reduces hepatocellular carcinoma by promoting semaphorin 6A mRNA
Song-Man Yu1, Min Zhang1, Sha-Lin Li1
1Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Background:
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with a poor prognosis, which is often associated with chronic hepatitis B virus infection in China. Our previous study has shown that long non-coding RNA semaphorin 6A-antisense RNA 1 (SEMA6A-AS1) was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.
Aim:
To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.
Methods:
The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction, immunohistochemistry and Western blot. A growth curve, colony formation, wound-healing and transwell (with or without Matrigel) assays were respectively performed to assess the proliferation, migration and invasion abilities of HCC cells. Cell cycle and apoptosis assays were performed by flow cytometry. To investigate the potential mechanism underpinning SEMA6A-AS1, we utilized tagged RNA affinity purification, dual luciferase reporter assay and immunofluorescence.
Results:
Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression. SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level, high Edmondson-Steiner grade and poor prognosis. SEMA6A-AS1 significantly inhibited the proliferation, migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation. SEMA6A protein promoted the proliferation, migration and invasion of HCC cells by regulating the actin cytoskeleton.
Conclusion:
Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation. SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
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