Abstract:Background and Aims: Long non-coding RNAs (lncRNAs) participate in a series of biological process such as cell proliferation, apoptosis, cell cycle control, cell development and differentiation, and their differential expressions are closely related to the occurrence and development of tumors. LncRNA RAB1A-2 (RAB1A-2) is an activator for MTORC1, and was found to be attributed to aberrant DNA amplification, cell proliferation and invasion in lung cancer cells. For further understand its biological functions, this study was conducted to investigate the expression and function of RAB1A-2 in gastric cancer.
Methods: The expressions of RAB1A-2 in 68 pairs of gastric cancer samples along with their adjacent noncancerous tissues, as well as in three gastric cancer cell lines (MKN-45, BGC-823, SGC-7901) and normal gastric mucosa cell line (GES-1) were detected by qRT-PCR. The relations of the expression of RAB1A-2 with clinicopathologic factors of gastric cancer patients were analyzed. The relationship between the expression of RAB1A-2 and prognosis was determined by Kaplan-Meier survival analysis. Gastric cancer SGC-7901 cells were transfected with si-RAB1A-2 (RAB1A-2 interference group), RAB1A-2 mimics (RAB1A-2 mimics group) and negative control sequences (negative control group), respectively. Then, the cell proliferation, apoptosis, and cell invasion ability were tested by MTT assay, flow cytometry, and Transwell assay, respectively.
Results: The results of qRT-PCR showed that expression levels of RAB1A-2 in gastric cancer tissue was significantly higher than that in adjacent noncancerous tissues, and in the three gastric cancer cell lines were significantly higher than that in normal gastric mucosa cell line (all P<0.05). The expression of RAB1A-2 was significantly associated with tumor size, T classification, N classification and TNM stage (all P<0.05). Survival analysis showed that both 3- and 5-year overall survival rates in patients with high RAB1A-2 expression were lower than those in patients with low RAB1A-2 expression group (both P<0.05). Compared with the SGC-7901 cells in negative control group, the A450 nm values at 24, 48 and 72 h after transfection were significantly increased in the SGC-7901 cells in RAB1A-2 mimics group, and were significantly decreased in the SGC-7901 cells in RAB1A-2 interference group (all P<0.05); the apoptosis rate was significantly reduced in the SGC-7901 cells in RAB1A-2 mimics group and was significantly increased in the SGC-7901 cells in RAB1A-2 interference group (both P<0.05); the number of invading cells was significantly increased in the SGC-7901 cells in RAB1A-2 mimics group and was significantly reduced in the SGC-7901 cells in RAB1A-2 interference group (both P<0.05).
Conclusion: RAB1A-2 expression is up-regulated in gastric cancer tissue and cells, and RAB1A-2 can promote the proliferation and invasion of gastric cancer cells and inhibit apoptosis. The gastric cancer patients with high RAB1A-2 expression may face a poor prognosis.