LncRNA COL1A1-014 is involved in the progression of gastric cancer via regulating CXCL12-CXCR4 axis
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ORIGINAL ARTICLE
LncRNA COL1A1‑014 is involved in the progression of gastric cancer via regulating CXCL12‑CXCR4 axis Xian‑Zhe Dong1 · Zi‑Run Zhao2 · Yuan Hu3 · Yu‑Pan Lu3 · Ping Liu3,4 · Lan Zhang1 Received: 26 March 2019 / Accepted: 3 October 2019 © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019
Abstract Background The aberrant expression of long noncoding RNAs (lncRNAs) is found in various types of cancers and also showed its association with the occurrence and development of gastric cancer (GC). We found lncRNA COL1A1-014 was frequently upregulated in GC. Methods This study investigated COL1A1-014 for its biological function at both cellular and animal levels, using MTT, flow cytometry, colony formation and transwell assays. The expression levels of COL1A1-014 and other genes were detected by RT-PCR and western blot. Luciferase reporter assay was used to detect the potential binding of miR-1273h-5p to COL1A1014 and CXCL12. Results We found that COL1A1-014 was frequently upregulated in GC tissues as well as cells. COL1A1-014 increased cell proliferation, colony forming efficiency, migration ability, invasion ability, and weight and volume of grafted tumors, while reduced cell apoptosis. Overexpression of COL1A1-014 increased the mRNA expression of chemokine (CXCmotif) ligand (CXCL12) and high levels of CXCL12 and CXCR4 proteins in GC cells. The levels of miR-1273h-5p showed an inverse correlation with COL1A1-014 and CXCL12 in GC cells transfected with miR-1273h-5p. The mRNAs of wild-type COL1A1014 and CXCL12 showed reduction in HEK293 cells transfected with miR-1273h-5p. This suggested that COL1A1-014 functions as an efficient miR-1273h-5p sponge and as a competing endogenous RNA (ceRNA) to regulate CXCL12. The proliferative activity of COL1A1-014 on GC cells was blocked by CXCL12-CXCR4 axis inhibitor AMD-3100. Conclusions These findings demonstrated that COL1A1-014 play an important regulatory role in GC development by functioning as a ceRNA in regulating the CXCL12/CXCR4 axis via sponging miR-1273h-5p. Keywords Gastric cancer · Long non-coding RNAs · Competing endogenous RNA · CXCL12/CXCR4 axis
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10120-019-01011-0) contains supplementary material, which is available to authorized users. * Ping Liu [email protected] * Lan Zhang [email protected] 1
Department of Pharmacy, Xuanwu Hospital of Capital Medical University, 45 Changchun Road, Xicheng District, Beijing 100053, China
2
Renaissance School of Medicine at Stony Brook University, NY 11794, USA
3
Department of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China
4
Department of Clinical Pharmacology, General Hospital of Chinese PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
Introduction Gastric cancer (GC) is one of the most common malignancies in the world and is the second most frequent cause of cancer death [1]. Although the serum carcinoembryonic antigen (CEA), carbohydra
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