Knockdown of linc00152 inhibits the progression of gastric cancer by regulating microRNA-193b-3p/ETS1 axis

Abstract

Background: Gastric cancer (GC) is a serious threat for public health worldwide. Long non-coding RNA (lncRNA) linc00152 has been well reported to be an oncogene and a potential biomarker in multiple cancers including GC. However, the molecular mechanisms of linc00152 in GC development need to be further investigated. Methods: RT-qPCR assay was employed to detect the levels of linc00152, microRNA-193b-3p (miR-193b-3p) and ETS1 mRNA. ETS1 protein level was measured by western blot assay. Cell proliferative, migratory and invasive capacities were assessed by colony formation together with CCK-8 assays, transwell migration and invasion assays, respectively. Bioinformatics analyses and luciferase reporter assay were used to explore whether miR-193b-3p could interact with linc00152 or ETS1 3ʹUTR. The roles and molecular basis of linc00152 silence on the growth of GC xenograft tumors were tested in vivo. Results: Linc00152 expression was notably upregulated in GC tissues and cells. The proliferative, migratory and invasive abilities of GC cells were weakened by linc00152 depletion, miR-193b-3p overexpression or ETS1 knockdown. Linc00152 upregulation inhibited miR-193b-3p expression by direct interaction and abolished miR-193b-3p-mediated anti-proliferation, anti-migration and anti-invasion effects in GC cells. ETS1 was a target of miR-193b-3p and linc00152 could promote ETS1 expression by downregulating miR-193b-3p. In vivo experiments further validated that linc00152 knockdown inhibited the growth of GC xenograft tumors by upregulating miR-193b-3p and downregulating ETS1. Conclusion: Knockdown of linc00152 inhibited GC progression by sequestering miR-193b-3p from ETS1 in vitro and in vivo, elucidating a novel molecular mechanism of linc00152 in promoting GC carcinogenesis.

Roles of E-cadherin and Noncoding RNAs in the Epithelial–mesenchymal Transition and Progression in Gastric Cancer

“…According to this mechanism, lncRNAs often regulate E-cadherin and EMT by downregulating miRNAs and thus upregulating their target genes. Apart from the already mentioned HOTAIR, this mechanism was described for the oncogenic lncRNA, Linc00152, which directly inhibits the expression of miR-193b-3p and thus abolishes its anti-proliferative, anti-migration, and anti-invasive effects in GC, leading additionally to ETS1 upregulation [123]. LncRNA XIST is another example, which is expressed from the inactive X chromosome, acts as a sponge for miR-101, and modulates EZH2 in GC cells [124].…”

The circRNA circ_0000291 acts as a sponge of microRNA 326 to regulate E26 transformation‐specific sequence‐1 expression and promote breast cancer progression

“…21,38 It is reported that ETS1 is an oncogene and is overexpressed in diverse cancers, such as gastric cancer, ovarian cancer and BC. 22,39 Promoting parathyroid hormone-related protein gene expression is one of the important reasons for ETS1 to drive BC progression. 40 Likewise, ETS1 is also regulated by multiple miRNAs, such as © 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Figure 3 miR-326 was the target of circ_0000291 in breast cancer (BC).…”

Long non-coding RNA linc00152 acting as a promising oncogene in cancer progression

“…Linc00152 might also sponge miR-193a-3p, and thus, contribute to the upregulation of Mcl-1 expression [14]. In addition, linc00152 may promote cell proliferation and increase cell migration in gastric adenocarcinoma cells by sponging miR-193b-3p, and thus, upregulating ETS1 [15]. In another study, it was found that sponging of miR-139-5p by linc00152 up-regulated Notch1, which promoted cell proliferation, cell invasion, and migration in colorectal carcinoma cells [16].…”