Downregulation of SOX2-OT Prevents Hepatocellular Carcinoma Progression Through miR-143-3p/MSI2

Abstract

ObjectiveLncRNA SOX2-OT is involved in a variety of cancers. This study explored the effect of lncRNA SOX2-OT on hepatocellular carcinoma (HCC) cells.MethodsSOX2-OT expressions were detected in HCC tissues and normal tissues, normal cells, and HCC cells. The relationship between SOX2-OT and prognosis was analyzed by TCGA. After SOX2-OT expression was inhibited using siRNA, HCC cell malignant behaviors were evaluated. The subcellular localization of SOX2-OT in HCC cells was predicted and analyzed. The binding relationships among SOX2-OT, miR-143-3p, and MSI2 were analyzed by bioinformatics website, dual-luciferase assay, and RNA pull-down assay. The effect of miR-143-3p and MSI2 on the regulation of SOX2-OT on biological behaviors of HCC cells was confirmed by functional rescue experiments. The effect of SOX2-OT on the tumorigenicity of HCC was evaluated by subcutaneous tumorigenesis in nude mice.ResultsSOX2-OT was highly expressed in HCC cells and tissues. The prognosis was poor in HCC patients with high SOX2-OT expression. Downregulating SOX2-OT inhibited HCC cell malignant behaviors. SOX2-OT bound to miR-143-3p to promote MSI2 expression. Downregulating miR-143-3p or upregulating MSI2 averted the role of si-SOX2-OT in HCC cells. Nude mouse subcutaneous tumorigenesis showed that SOX2-OT downregulation decreased the tumorigenicity of HCC, and affected the levels of miR-143-3p and MSI2 mRNA in tumor tissues.ConclusionSOX2-OT inhibited the targeted inhibition of miR-143-3p on MSI2 through competitively binding to miR-143-3p, thus promoting MSI2 expression and proliferation, invasion, and migration of HCC cells.

Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report

“…High MSI2 levels were associated with poor tumor differentiation, and poor prognosis. Indeed, functional studies demonstrated a role of MSI2 in maintaining stemness properties, metastatic capacity, in vitro and in vivo tumorigenic ability and promoting drug resistance either in HCC or pancreatic tumors [ 33 , 34 , 35 , 36 ]. Interestingly, in pancreatic cancer, a high proportion of circulating tumor cells (CTCs) expressed Msi2 (Msi2+), and were more tumorigenic than Msi2− CTCs, posing a greater risk for tumor dissemination [ 33 ].…”

Biological functions and potential mechanisms of miR‑143‑3p in cancers (Review)

“…miR-143-3p is also a target of the lncRNA SOx2-OT, and its expression levels are negatively correlated. The lncRNA SOx2-OT competitively binds with miR-143-3p to promote the expression of Musashi RNA binding protein 2 (MSI2) and consequently promote the malignant progression of HCC ( 31 ). Another study showed that the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is highly expressed in HCC tissues and binds to miR-143-3p to inhibit miR-143-3p expression; subsequently, miR-143-3p accelerates the progression of HCC by regulating zinc finger E-box binding homeobox 1 (ZEB1) expression ( 32 ).…”

Zooming in on Long Non-Coding RNAs in Ewing Sarcoma Pathogenesis

“…LncRNA SOX2 Overlapping Transcript (Sox2OT) is highly expressed in several cancers and has been associated with unfavorable prognosis in those cancers where it was found to promote migration and invasion through diverse mechanisms [105][106][107]. Sox2OT has been mapped to 3q26.3-q27 chromosomal locus in humans, demonstrated to harborat least eight transcript variants and is abundantly expressed in embryonic stem cells [108,109].…”