The Role of miR-1183: A Potential Suppressor in Hepatocellular Carcinoma via Regulating Splicing Factor SRSF1

Abstract

Zhilu Yao,1,2,* Ning Liu,3,* Hui Lin,1 Yingqun Zhou2,4 1Department of Gastroenterology, Jingan District Zhabei Central Hospital, Shanghai, 200072, People’s Republic of China; 2Clinical Medical College of Shanghai Tenth People’s Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 3Department of Gastroenterology, Changzhou Maternal and Child Health Hospital, Changzhou, 213004, People’s Republic of China; 4Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingqun Zhou; Hui Lin, Email [email protected]; [email protected]: Hepatocellular carcinoma (HCC) is a severe global health problem, causing many deaths of patients all over the world. Serine and arginine-rich splicing factor 1 (SRSF1) functions as an important oncogenic role in tumorigenesis and progression in HCC. Therefore, therapies targeting SRSF1 may provide promising therapeutic approaches. MiRNAs are virtually involved at the post-transcriptional level and bind to 3’ untranslated region (3’-UTR) of their target messenger RNA (mRNA) to suppress expression.Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of SRSF1 and miR-1183 in HCC cell lines. CCK8 assay, colony formation assay and wound healing assay were used to detect the function of miR-1183 in HCC cell lines in vitro. Luciferase reporter assay and Western blot were applied to detect the regulation of particular molecules. Xenograft tumor assay was used to detect the function of miR-1183 in HCC cell lines in vivo. Immunohistochemistry (IHC) was used to detect the expression of SRSF1 in HCC tissues and Xenograft tumors.Results: In this study, we identified that miR-1183 was downregulated in HCC cell lines. Functional assays indicated that miR-1183-upregulation cells show weakened proliferation ability and migration ability in vitro and inhibit subcutaneous tumor formation in vivo. With respect to the underlying mechanism, we found that miR-1183 function as a tumor suppressor by specifically binding to SRSF1.Conclusion: This study is the first to demonstrate that miR-1183 function as an important tumor-suppressing role by binding to the 3’-UTR of SRSF1 mRNA and suppressing its protein level in HCC cells in vitro and in vivo. Further, miR-1183 may be a potential target in the prognosis and treatment of HCC.Keywords: SRSF1, miR-1183, HCC, proliferation, migration

Keywords

• srsf1
• mir-1183
• hcc
• proliferation
• migration