The long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. However, the function of lncRNAs and the role of lncRNAs in gastric cancer remain to be determined. Herein, the function of lncRNA CA3-AS1 was investigated in gastric cancer. Firstly, we found that the expression level of CA3-AS1 was decreased in gastric cancer cell lines and tissues. Then, CA3-AS1 overexpression inhibited the gastric cancer cells migration and invasion and knockdown of CA3-AS1 enhanced the gastric cancer cells migration and invasion. Moreover, FISH assays and qPCR results revealed that CA3-AS1 was mainly expressed in the cytoplasm of gastric cancer cells. Then, the relationship between CA3-AS1 and miR-93-5p was explored. Luciferase reporter assays results showed that miR-93-5p was a direct target of CA3-AS1 in SGC-7901 and BCG-823. Furthermore, BTG3 was identified as a direct target gene of miR-93-5p. Restore experiments showed that CA3-AS1 upregulated the expression level of BTG3 and inhibited the gastric cancer cells invasion by sponging miR-93-5p. Finally, we found that CA3-AS1 inhibited the metastasis ability of gastric cancer cells in vivo. Above results suggested that CA3-AS1 acted as anti-oncogene in gastric cancer and might become a vital target for clinical treatment.
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Tan P, Yeoh KG. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 2015;149:1153–62.e3.
Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, et al. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14:e535–47.
Li Y, Sun Q, Jiang M, Li S, Zhang J, Xu Z, et al. KLF9 suppresses gastric cancer cell invasion and metastasis through transcriptional inhibition of MMP28. FASEB J. 2019;33:7915–28.
Li ZY, Zhang QW, Zhang CH, Teng LM, Huang Y. Comparable rates of lymph node metastasis and survival between the diffuse-type and intestinal-type early gastric cancer patients: a large population-based study. Gastrointest Endosc. 2019;90:84–95.e10.
Xu Y, Yao Y, Jiang X, Zhong X, Wang Z, Li C, et al. SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma. J Exp Clin Cancer Res CR. 2018;37:81.
Li Q, Dong C, Cui J, Wang Y, Hong X. Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. J Exp Clin Cancer Res CR. 2018;37:265.
Wang X, Kan J, Han J, Zhang W, Bai L, Wu H. LncRNA SNHG16 functions as an oncogene by sponging MiR-135a and promotes JAK2/STAT3 signal pathway in gastric cancer. J Cancer. 2019;10:1013–22.
Jiang D, Li H, Xiang H, Gao M, Yin C, Wang H, et al. Long chain non-coding RNA (lncRNA) HOTAIR knockdown increases miR-454-3p to suppress gastric cancer growth by targeting STAT3/Cyclin D1. Med Sci Monit Int Med J Exp Clin Res. 2019;25:1537–48.
Zhang J, Jin HY, Wu Y, Zheng ZC, Guo S, Wang Y, et al. Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1. Clin Transl Oncol. 2019;21:1142–51.
Huang W, Liu Z, Li Y, Liu L, Mai G. Identification of long noncoding RNAs biomarkers for diagnosis and prognosis in patients with colon adenocarcinoma. J Cell Biochem. 2019;120:4121–31.
Wei H, Yang Z, Lin B. Overexpression of long non coding RNA CA3-AS1 suppresses proliferation, invasion and promotes apoptosis via miRNA-93/PTEN axis in colorectal cancer. Gene. 2019;687:9–15.
Wang Q, Wang J, Niu S, Wang S, Liu Y, Wang X. MicroRNA-664 targets paired box protein 6 to inhibit the oncogenicity of pancreatic ductal adenocarcinoma. Int J Oncol. 2019;54:1884–96.
Jiang F, Yu Q, Chu Y, Zhu X, Lu W, Liu Q, et al. MicroRNA-98-5p inhibits proliferation and metastasis in non-small cell lung cancer by targeting TGFBR1. Int J Oncol. 2019;54:128–38.
Dong X, He X, Guan A, Huang W, Jia H, Huang Y, et al. Long non-coding RNA Hotair promotes gastric cancer progression via miR-217-GPC5 axis. Life Sci. 2019;217:271–82.
Ma DH, Li BS, Liu JJ, Xiao YF, Yong X, Wang SM, et al. miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway. Cancer Lett. 2017;408:23–32.
Wang SJ, Cao YF, Yang ZQ, Jiang ZY, Cai B, Guo J, et al. MicroRNA-93-5p increases multidrug resistance in human colorectal carcinoma cells by downregulating cyclin dependent kinase inhibitor 1A gene expression. Oncology Lett. 2017;13:722–30.
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012;13:607–15.
Group G, Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303:1729–37.
Gruen RL, Pitt V, Green S, Parkhill A, Campbell D, Jolley D. The effect of provider case volume on cancer mortality: systematic review and meta-analysis. CA Cancer J Clin. 2009;59:192–211.
Wang S, Ni B, Zhang Z, Wang C, Wo L, Zhou C, et al. Long non-coding RNA DNM3OS promotes tumor progression and EMT in gastric cancer by associating with Snail. Biochem Biophys Res Commun. 2019;511:57–62.
Li H, Wang Y. Long noncoding RNA (lncRNA) MIR22HG suppresses gastric cancer progression through attenuating NOTCH2 signaling. Med Sci Monit Int Med J Exp Clin Res. 2019;25:656–65.
Zhang Y, Li Q, Yu S, Zhu C, Zhang Z, Cao H, et al. Long non-coding RNA FAM84B-AS promotes resistance of gastric cancer to platinum drugs through inhibition of FAM84B expression. Biochem Biophys Res Commun. 2019;509:753–62.
Ding Z, Lan H, Xu R, Zhou X, Pan Y. LncRNA TP73-AS1 accelerates tumor progression in gastric cancer through regulating miR-194-5p/SDAD1 axis. Pathol Res Pract. 2018;214:1993–9.
Zhou Z, Lin Z, He Y, Pang X, Wang Y, Ponnusamy M, et al. The long noncoding RNA D63785 regulates chemotherapy sensitivity in human gastric cancer by targeting miR-422a. Mol Ther Nucleic Acids. 2018;12:405–19.
Zhao X, Wang D, Ding Y, Zhou J, Liu G, Ji Z. lncRNA ZEB1-AS1 promotes migration and metastasis of bladder cancer cells by post-transcriptional activation of ZEB1. Int J Mol Med. 2019;44:196–206.
An Q, Zhou Y, Han C, Zhou Y, Li F, Li D. BTG3 overexpression suppresses the proliferation and invasion in epithelial ovarian cancer cell by regulating AKT/GSK3beta/beta-catenin signaling. Reprod Sci. 2017;24:1462–8.
Du Y, Liu P, Zang W, Wang Y, Chen X, Li M, et al. BTG3 upregulation induces cell apoptosis and suppresses invasion in esophageal adenocarcinoma. Mol Cell Biochem. 2015;404:31–8.
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Zhang, X., Zhuang, H., Wang, J. et al. Long noncoding RNA CA3-AS1 suppresses gastric cancer migration and invasion by sponging miR-93-5p and targeting BTG3. Gene Ther (2020). https://doi.org/10.1038/s41434-020-00201-1