Long Non-Coding RNA CASC2 Functions as A Tumor Suppressor in Colorectal Cancer via Modulating The miR-18a-5p/BTG3 Pathway

Abstract

Objective: Reportedly, long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved inregulating colorectal cancer (CRC) progression. However, the function and detailed downstream mechanism of CASC2in CRC progression are not fully elucidated. The aim of the study was to investigate the potential function and molecularmechanism of CASC2 in CRC progression.Materials and Methods:In this experimental study, quantitative real-time polymerase chain reaction (qRT-PCR) wasadopted to probe CASC2, microRNA-18a-5p (miR-18a-5p) and B cell translocation gene 3 (BTG3) mRNA expressionin CRC tissues and cell lines. After CASC2 was overexpressed in Colo-678 and HCT116 cell lines, methylthiazoltetrazolium (MTT) and 5-bromo-2’-deoxyuridine (BrdU) assays were employed to examine the proliferation of CRC cells.Transwell migration and invasion assays were executed to evaluate the metastatic potential of CRC cells. The targetingrelationships among CASC2, miR-18a-5p and BTG3 were validated by dual luciferase reporter gene assay. Westernblot assay was applied to examine the regulatory effects of CASC2 and miR-18a-5p on BTG3 protein expression.Results:CASC2 was decreased in CRC tissues and cell lines, and its low expression in CRC tissues was associatedwith larger tumor size and lymph node metastasis. CASC2 overexpression restrained proliferative, migrative andinvasive capabilities of CRC cells. CASC2 could function as a molecular sponge for miR-18a-5p and repress theexpression of miR-18a-5p. Furthermore, the inhibitory effects of CASC2 on the malignant phenotypes of CRC cells wascounteracted by miR-18a-5p mimics. Additionally, CASC2 could positively regulate BTG3 expression via suppressingmiR-18a-5p.Conclusion: CASC2 inhibits CRC development by suppressing miR-18a-5p and raising BTG3 expression.

Keywords

• b cell translocation gene 3
• colorectal cancer
• lncrna casc2
• mir-18a-5p