LncRNA GAS8-AS1 regulates cancer cell proliferation and predicts poor survival of patients with gastric cancer.

Abstract

Long non-coding (lnc)RNAs have been recognized as important regulators in gastric cancer. lncRNA GAS8-AS1 is considered a tumor suppressor in multiple types of cancer, such as papillary thyroid carcinoma, ovarian cancer and colorectal cancer. However, the specific role of GAS8-AS1 in gastric cancer remains to be fully elucidated. The aim of the present study was to investigate the role of GAS8-AS1 in gastric cancer and its potential underlying mechanisms of action. The expression levels of GAS8-AS1, microRNA (miR)-21-3p, PTEN and pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in gastric cancer and non-cancerous tissues, as well as in gastric cancer cell lines, were detected using reverse transcription-quantitative PCR. Cell proliferation was detected by using a Cell Counting Kit-8 assay. Cell migration and invasion were detected using a Transwell assay. Results of the present study demonstrated that the expression levels of GAS8-AS1 in gastric cancer tissues were significantly decreased, whereas its expression did not differ among cancer tissues at different clinical stages. Low expression levels of GAS8-AS1 predicted poor 5-year survival rates for 70 patients with gastric adenocarcinoma from the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) during patient follow-up. In addition, the expression levels of miR-21-3p were markedly increased in cancer tissues, and miR-21-3p expression was negatively associated with the expression of GAS8-AS1. The direct interaction between GAS8-AS1 and miR-21-3p was predicted using the starBase database and was confirmed by using an RNA pull-down assay. In gastric cell lines, the overexpression of GAS8-AS1 reduced the expression levels of mature miR-21-3p but did not affect the expression of miR-21-3p precursor, while the overexpression of miR-21-3p did not, in turn, affect the expression of GAS8-AS1. In addition, the overexpression of GAS8-AS1 inhibited cancer cell proliferation, while the overexpression of miR-21-3p promoted cancer cell proliferation and attenuated the effects of GAS8-AS1. Overexpression of miR-21-3p promoted cancer cell migration and invasion, whereas overexpression of GAS8-AS1 did not affect cell migration or invasion. In summary, results of the present study have demonstrated that GAS8-AS1 acts as a tumor suppressor in gastric cancer, and it may inhibit cancer cell proliferation by downregulating miR-21-3p.