Male-specific long non-coding RNA testis-specific transcript, Y-linked 15 promotes gastric cancer cell growth by regulating Wnt family member 1/ß-catenin signaling by sponging microRNA let-7a-5p.

The present study is aimed to investigate the regulatory effects and related mechanism of long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) in gastric carcinoma (GC) cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT). TTTY15 expression in GC tissue samples and cells was detected by quantitative real-time PCR (qRT-PCR), and the correlation between TTTY15 expression and GC clinicopathological indicators was analyzed. Cell counting kit-8 (CCK-8), BrdU, flow cytometry and Transwell assays were performed for detecting GC cell proliferation, migration, invasion and apoptosis. Western blot was performed for detecting the expressions of EMT-associated proteins (N-cadherin and E-cadherin), Wnt family member 1 (Wnt1) protein and ß-catenin protein. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation (RIP) assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of microRNA let-7a-5p (let-7a-5p) with TTTY15 and Wnt1 mRNA 3'UTR. It was found that TTTY15 expression was significantly up-regulated in GC tissues and cells, and was associated with advanced TNM stage and poor tumor differentiation. TTTY15 overexpression promoted GC cell proliferation, migration and invasion, the expressions of N-cadherin, Wnt1 and ß-catenin protein, and inhibited the apoptosis and E-cadherin expression, while knocking down TTTY15 had the opposite effects. TTTY15 directly targeted let-7a-5p and negatively regulated its expression. Wnt1 was the target gene of let-7a-5p, and TTTY15 could indirectly and positively regulate Wnt1 expression. In conclusion, TTTY15 promotes GC progression, by regulating the let-7a-5p/Wnt1 axis to activate the Wnt/ß-catenin pathway.

MALAT1 overexpression promotes the growth of colon cancer by repressing ß-catenin degradation.

Colon cancer is one of the most common types of cancer and more than 80% of colon cancer cases are associated with Wnt-ß-catenin signaling activation. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a multi-functional long non-coding RNA that is overexpressed in many types of cancers, including colon cancer. In this study, MALAT1 and ß-catenin were found to be overexpressed in tumor samples from 62 patients with colon cancer. A positive correlation was identified between MALAT1 levels and ß-catenin protein levels in tumors. MALAT1 was found to upregulate ß-catenin protein levels in HCT116 and LOVO cells without changing the mRNA expression levels. ß-catenin degradation was confirmed to be upregulated in MALAT1-knockdown cells and inhibited in cells overexpressing MALAT1 overexpressing. MALAT1 was then identified as a negative regulator of GSK-3ß; it did so via promotion of H3K27 trimethylation of the promoter region. In conclusion, MALAT1 is an oncogene in colon cancer, which inhibits ß-catenin degradation by upregulating H3K27 trimethylation and repressing GSK-3ß expression.