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Abstract
Gastric cancer (GC) is one of the most common malignancy and the third leading cancer-related death in China. Long noncoding RNAs (lncRNAs) have been implicated in numerous tumors, including GC, however, the mechanism of many functional lncRNAs is still unclear. In this study, we identified the abundantly expressed lncRNA, RP11-290F20.3, in GC cells and patient tumor tissues. We named this lncRNA as GC-related lncRNA1 (GCRL1), which could regulate gastric cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, miRNA-885-3p (miR-885-3p) could inhibit the cell proliferation and metastasis in GC by negatively regulating the expression of cyclin-dependent kinase 4 (CDK4) at the post-transcriptional level. Further, GCRL1 promoted the cell proliferation and metastasis by sponging miR-885-3p and hence, positively regulating CDK4 in GC cells. Taken together, our results demonstrate a novel regulatory axis of malignant cell proliferation and invasion in GC, comprising GCRL1, miR-885-3p, and CDK4, which may serve as a potential therapeutic target in GC.
Highlights
Gastric cancer (GC) is a common malignancy worldwide and one of the top leading causes of cancer mortality in China[1,2]
Bioactive long ncRNAs (lncRNAs) activated in renal clear cell carcinoma (RCC) with Sunitinib resistance incorporated into exosomes has been reported to induce resistance to Sunitinib when transferred to drug-sensitive cells, mainly by competitively binding to miR-34/miR-449 for enhancing the expression of AXL and c-MET expression in RCC cells[47]
Our results confirmed that GC-related lncRNA1 (GCRL1) could act as upstream regulator for miR-885-3p and promoted proliferation and metastasis in GC cells
Summary
Gastric cancer (GC) is a common malignancy worldwide and one of the top leading causes of cancer mortality in China[1,2]. Its molecular mechanisms are very complicated and still poorly understood[3,4]. It is an urgent clinical need to explore the underlying molecular mechanisms of GC proliferation and metastasis, to find specific markers or to set up precise and less harmful strategies for this disease. Some miRNAs are reported to be involved in the modulation of the biological behaviors of tumor cells such as cell growth, invasion, autophagy, and apoptosis[12,13,14]. MiR-29c is reported to be one of the lowest expressed miRNAs in GC tissues and could suppress cancer cell migration and induce apoptosis by directly targeting integrin β1 (ITGB1)[14]. LncRNAs are Official journal of the Cell Death Differentiation Association
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