Down regulation of lncRNA MEG3 promotes colorectal adenocarcinoma cell proliferation and inhibits the apoptosis by up-regulating TGF-β1 and its downstream sphingosine kinase 1

摘要

OBJECTIVE: LncRNA MEG3 is involved in the pathogenesis of several types of cancers. While its participation and function network in colorectal (CR) adenocarcinoma, which is one of the most common malignancies, still hasn’t been well studied. Therefore, our study aimed to investigate the role of MEG3 in colorectal adenocarcinoma and to explore the possibly related mechanisms. PATIENTS AND METHODS: Tumor tissues and adjacent healthy tissues were collected from colorectal adenocarcinoma patients. Blood samples were collected from both colorectal adenocarcinoma patients and healthy controls to prepare serum sample. Expression of MEG3 in those tissues was detected by qRT-PCR. MEG3 knockdown and sphingosine kinase 1 (SPHK1) overexpression colorectal adenocarcinoma cell lines were established. Its effects on cell proliferation and apoptosis were investigated by CCK-8 assay and MTT assay, respectively. Effects of MEG3 overexpression on TGF-β1 and SPHK1 were investigated by Western blot. RESULTS: MEG3 expression level was decreased in tumor tissues than that in adjacent healthy tissues. Serum level of MEG3 was lower in cancer patients than that in healthy controls, and the serum level decreased with the increased stage of primary tumor. Serum TGF-β1 can be used to predict colorectal adenocarcinoma and its prognosis accurately. MEG3 knockdown and SPHK1 overexpression promoted tumor cell proliferation, but inhibited cell apoptosis. MEG3 knockdown also increased the expression level of TGF-β1 and SPHK1. Treatment with TGF-β1 inhibitor reduced the expression level of SPHK1 but showed no significant effects on MEG3. SPHK1 overexpression showed no significant effects on MEG3 and TGF-β1 expression. CONCLUSIONS: Downregulation of lncRNA MEG3 can promote colorectal adenocarcinoma cell proliferation and inhibit the apoptosis by up-regulating TGF-β1 and its downstream sphingosine kinase 1.