Long non-coding RNA TTTY15 silencing inhibits gastric cancer progression by sponging microRNA-98-5p to down-regulate cyclin D2 expression

Abstract

Gastric cancer is the most common malignant tumor in the digestive system. However, the detection rate of early gastric cancer is low, resulting in delayed prognosis and poor outcomes. The identification of effective therapeutic targets for gastric cancer is, therefore, of profound significance. Recently, various lncRNAs have been shown to be biomarkers for different cancers. This study investigated the role of long non-coding RNA (lncRNA) TTTY15 in gastric cancer. The expression level of TTTY15, miR-98-5p , and cyclin D2 ( CCND2 ) were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot assay using tumor and non-tumor tissues collected from 30 patients with gastric cancer, gastric cancer cell lines (AGS, SNU-5, and NCI-N87), and the normal gastric epithelial cell line GES-1. The interaction between TTTY15 and miR-98-5p and between miR-98-5p and CCND2 were predicted by bioinformatics and then further verified by dual-luciferase and RNA pull-down analyses. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay, and apoptosis was measured using flow cytometry and caspase-3 assay. The results indicate that TTTY15 and CCND2 expression increased and miR-98-5p expression decreased in gastric cancer tumor tissues and cell lines. TTTY15 knockdown inhibited gastric cancer cell proliferation but promoted apoptosis by sponging miR-98-5p , which acted as a tumor suppressor gene by reducing the expression of its target gene CCND2 in gastric cancer. In conclusion, lncRNA TTTY15 is a potential oncogene involved in gastric cancer and may be a novel therapeutic target for gastric cancer treatment.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

“…In our panel, HAR1A also acted as a negative factor for early lymph node metastasis in GC. Similarly, TP53TG1 and TTTY15 have been con rmed to be differentially expressed in GC tissues compared with that in normal gastric mucosa [25,35]. Finally, as biomarkers, each lncRNA in our panel was endowed with an additional diagnostic coe cient and made a signi cant contribution to the identi cation of LN metastasis.…”

“…LncRNAs are mRNA-like transcripts of >200 nucleotides with no capacity to encode proteins (21). A variety of cancers show abnormal expression of lncRNAs, which have diverse functions in gene regulation, cell biological behavior, and tumor initiation and progression [25,26]. To date, there have been a considerable number of studies on lymph node metastasis of GC; however, most of them explored the regulatory mechanism of a single lncRNA [27,28].…”

Identification of m6A/m5C-related lncRNA signature for prediction of prognosis and immunotherapy efficacy in esophageal squamous cell carcinoma

“…Furthermore, the male Y chromosome-linked lncRNAs TTTY15 assume a crucial role in carcinogenesis across diverse cancer types. Acting as an RNA sponge, TTTY15 engages several miRNAs to promote cancer progression, exemplified by its interaction with miR-29-3p in colorectal cancer 33 , miR-98-5p 34 and miRNA let-7a-5p 35 in gastric cancer. In prostate cancer, TTTY15 exhibits prominent upregulation in most tumor samples, exerting a pro-carcinogenic influence by sponging miRNA let-7, subsequently elevating CDK6 and FN1 expression 36 .…”

Application of angiogenesis-related genes associated with immune infiltration in the molecular typing and diagnosis of acute myocardial infarction

“…For example, Zhu et al found that lncRNA RP11-805J14.5 can compete with CCND2 for miR-34b-3p and miR-139-5p in lung adenocarcinoma [ 40 ]. Wen et al suggested that regulating the TTTY15/miR-98-5p/CCND2 axis may inhibit the progression of gastric cancer [ 41 ]. Salem et al reported that miR-590-3p contributes to ovarian cancer growth and metastasis by stimulating the FOXA2 vesicant pathway [ 42 ].…”