LncRNA LINC00483 promotes gastric cancer development through regulating MAPK1 expression by sponging miR-490-3p

Abstract

Background: Previous studies have shown that long noncoding RNA (lncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this lncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1). Methods:Thirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo.Results: LINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis. Conclusion:Knockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR-490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.

LINC00689 induces gastric cancer progression via modulating the miR‐338‐3p/HOXA3 axis

“…Recently, new non-coding RNAs lncRNAs have been reported to be involved in the initiation and advancement of gastric cancer. 22,29,30 For example, Luo et al 31 showed that LINC00483 was overexpressed in gastric cancer cells and tissues and LINC00483 knockdown suppressed cell invasion, viability and migration and induced apoptosis partly by modulating MAPK1/miR-490-3p axis. Zhang et al 32 reported that FTX was up-regulated in gastric cancer specimens and cells and elevated the expression of the FTX-induced cell cycle and proliferation via targeting miR-215.…”

LncRNA NUTM2A‐AS1 positively modulates TET1 and HIF‐1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR‐376a

“…So far, a number of evidence show that lncRNAs are involved in tumor progression and cisplatin resistance of gastric cancer via various mechanisms. [25][26][27][28] NUTM2A-AS1 has not been studied in cancer, including gastric cancer. Our group, for the first time, prove that NUTM2A-AS1 accelerates tumor invasion, angiogenesis, and cisplatin resistance at cellular and animal level.…”

“…So far, a number of evidence show that lncRNAs are involved in tumor progression and cisplatin resistance of gastric cancer via various mechanisms 25‐28 . NUTM2A‐AS1 has not been studied in cancer, including gastric cancer.…”

miR‐490: A potential biomarker and therapeutic target in cancer and other diseases

“…miR‐490 was found to be downregulated in different cancer types and its functional analysis, wherever reported, identified its role majorly as a tumor‐suppressive miRNA (Table 1). Interestingly, the extent of its downregulation has been correlated with increased tumor progression of acute myeloid leukemia (C. Wang et al, 2020), bladder cancer (Han et al, 2011; Lan et al, 2015; Li et al, 2013; Wei et al, 2016; L. Wu et al, 2019; Xiang et al, 2019; Zhang, Wang, et al, 2019), breast cancer (Fan et al, 2020; Jia et al, 2016; Tao et al, 2018; Zhao & Zheng, 2016), cholangiocarcinoma (Leng et al, 2019), colorectal cancer (Hamfjord et al, 2012; Liu et al, 2018; X. Xu et al, 2015; Zheng et al, 2016), digestive cancers (Tang et al, 2016), endometrial cancer (Shao et al, 2018; Sun et al, 2015), esophageal squamous cell carcinoma (Kang et al, 2018; Li & Zang, 2019; Pan et al, 2019; Zabihula et al, 2019), Ewing's sarcoma (Nakatani et al, 2012), gastric cancer (Luo & Liang, 2020; Qu et al, 2017; Shen et al, 2015; Zhang, Ma, et al, 2019; Zhou et al, 2016), glioblastoma (Giunti et al, 2019; Vinchure et al, 2019; F. Zhang et al, 2019; Zhao et al, 2018), hepatocellular carcinoma (Cai et al, 2018; Chen et al, 2017, 2019; Dai et al, 2019; Ding et al, 2020; Dou et al, 2017; Fang et al, 2018; Li et al, 2018; Wang et al, 2018; Wojcicka et al, 2014; Xu et al, 2017, 2018; Yu et al, 2019; H. Zhang et al, 2020; Zheng et al, 2018), lung cancer (Dong et al, 2020; Gu et al,…”

“…Specific lncRNAs were found to be directly targeted by miR‐490 in various cancers. These include lncRNAs CCAT1 (Dou et al, 2017; hepatocellular carcinoma), TONSL‐AS1 (Liu et al, 2020; ovarian epithelial carcinoma), LINC00483 (Luo & Liang, 2020; gastric cancer), SNHG6 (Dong et al, 2020; non‐small cell lung cancer), LINC00173 (Fan et al, 2020; breast cancer), BCYRN1 (Ding et al, 2020; hepatocellular carcinoma), RP11‐81H3.2 (Chen et al, 2019; hepatocellular carcinoma), XLOC_001659 (Li & Zang, 2019; esophageal squamous cell carcinoma), SNHG15 (Dai et al, 2019; hepatocellular carcinoma), and DLEU1 (Wang et al, 2017; ovarian carcinoma).…”