Long noncoding RNA HCG18 up‐regulates the expression of WIPF1 and YAP/TAZ by inhibiting miR‐141‐3p in gastric cancer

Abstract

Background Accumulating works show that lncRNAs play critical roles in the development of gastric cancer (GC). LncRNA HLA complex group 18 (HCG18) was implicated in the progression of bladder cancer and glioma, but its role in GC is unknown. Methods RT‐PCR was used to detect HCG18 and miR‐141‐3p expression in GC specimen. GC cell lines (AGS and MKN‐28) were exploited as cell model. The biological effect of HCG18 on cancer cells was probed by CCK‐8, colony formation, flow cytometry, Transwell and wound‐healing experiments in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Interaction between HCG18 and miR‐141‐3p was determined by bioinformatics analysis, RT‐PCR, and luciferase reporter experiments. Downstream gene expression of miR‐141‐3p, including Wiskott–Aldrich syndrome protein interacting protein family member 1 (WIPF1), Yes associated protein 1 (YAP), and tafazzin (TAZ) were detected using Western blot. Results HCG18 was markedly up‐regulated in GC specimens, while miR‐141‐3p was markedly down‐regulated. Down‐regulation of HCG18 inhibited viability, migration, and invasion of GC cells, while miR‐141‐3p transfection led to opposite effect. HCG18 could down‐regulate miR‐141‐3p through adsorbing it, and a negative association between HCG18 and miR‐141‐3p was found in GC specimens. HCG18 promoted WIPF1, YAP and TAZ expression, nonetheless, such influence was reversed by co‐transfecting with miR‐141‐3p. Conclusion HCG18 was aberrantly up‐regulated in GC tissues, and it indirectly regulated the activity of Hippo signaling through counteracting miR‐141‐3p expression.

Identification of HCG18 and MCM3AP-AS1 That Associate With Bone Metastasis, Poor Prognosis and Increased Abundance of M2 Macrophage Infiltration in Prostate Cancer

“…Knockdown of HCG18 inhibited the proliferation, migration, invasion, metastasis, while induced the apoptosis of cancer cells. [31][32][33]36,37 Also, silencing of HCG18 suppressed the growth of xenografts in mice. 36 Mechanistically, HCG18 was reported to competitively bind to miR-140, 31 miR-214-3p, 32 miR-1271, 33 miR-34a-5p 35 and miR-152-3p 34 to respectively enhance the expressions of the target genes of these miRNAs, including cyclin D1, CENPM, MTDH, HMMR and DNAJB12.…”

Long non-coding RNA HCG18 promotes malignant phenotypes of breast cancer (BC) cells by HCG18/miR-103a-3p/UBE2O/mTORC1/HIF-1α positive feedback loop

“…Previously studies also reported that HCG18 played tumor promotor roles in many other types of carcinomatosis. HCG18 could increase the expression level of WIPF1, DNAJB12 and activate PI3K/AKT axis in gastric cancer cells, thus promoting gastric cancer progression 7,9,10 . HCG18 could contribute to hepatocellular carcinoma progression by improving CENPM expression 8 .…”

“…Previously studies have also reported that HCG18 has oncogenic functions in gastric cancer, hepatocellular carcinoma, lung adenocarcinoma and colorectal cancer. However, its biological function in human BC remains unclear [7][8][9][10] .…”

Construction of a ceRNA network in glioma and analysis of its clinical significance

“…HCG18 is overexpressed in gastric cancer and indirectly regulates Hippo signal transduction activity by inhibiting the expression of miR-141-3p [ 38 ]. It is also overexpressed in colorectal cancer tissues and cell lines and can enhance MTDH/Wnt/β-catenin signaling through the sponging of miR-1271, thereby exerting potential carcinogenic effects [ 39 ].…”