LncRNA TTN-AS1 contributes to gastric cancer progression by acting as a competing endogenous RNA of miR-376b-3p

Abstract

Long noncoding RNAs (lncRNAs) were reported to participate in the progression of gastric cancer (GC). However, little is known about the biological functions of TTN antisense RNA 1 (TTN-AS1) in GC. Using qRT-PCR examination, we found that TTN-AS1 was expressed at a higher level in GC tissues and cell lines compared to the normal controls. Kaplan-Meier analysis of GC patients revealed the negative correlation between TTN-AS1 expression and the overall survival. To detect the biological function of TTN-AS1 in GC, we silenced TTN-AS1 to perform loss-of-function assays. The experimental results revealed that knockdown of TTN-AS1 obviously inhibited GC cell proliferation, induced cell apoptosis and impaired cell migration and invasion. In mechanism, TTN-AS1 was located in the cytoplasm of GC cells, indicating the post-transcriptional regulation of TTN-AS1 on gene expression. Bioinformatics analysis revealed the potential binding relation between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12. Mechanism experiments such as luciferase reporter assay and RNA pull-down assay demonstrated the interaction between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12 in GC cells. At last, rescue assays certified that miR-376b-3p and KLF12 involved in TTN-AS1-mediated GC progression. Similarly, the role of TTN-AS1-miR-376b-3p-KLF12 axis in GC progression was analyzed and validated. Taken together, we concluded that TTN-AS1 might function as a novel potential therapeutic target in the treatment of gastric cancer.

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

“…Then, Cui et al verified that TTN-AS1 promoted proliferation, migration, invasion, and EMT in PTC 19 . Lately, Dong et al found that TTN-AS1 could promote the progression of gastric cancer via functioning as a ceRNA of miR-376b-3p to regulate KLF12 20 . Aiming at realizing the function of TTN-AS1 in LUAD, we first analyzed the expression of TTN-AS1 in LUAD with the help of TCGA database, the results showed that TTN-AS1 was a highly expressed lncRNA in LUAD.…”

“…TTN-AS1 has been identified to be an oncogene in numerous cancers, such as hepatocellular carcinoma, cervical cancer, papillary thyroid cancer, and gastric cancer [16][17][18][19][20] . Importantly, TTN-AS1 exerted regulating effects via functioning as a ceRNA to sponge different miRNAs [16][17][18][19][20] . For instance, TTN-AS1 facilitated the proliferation and metastasis ability of esophageal squamous cell carcinoma by the modulating miR-133b/FSCN1 axis 16 .…”

LncRNA TTN‑AS1 promotes endometrial cancer by sponging miR‑376a‑3p

“…TTN-AS1 enhanced lung cancer progression by regulating the PTEN/PI3K/AKT signaling pathway (28). TTN-AS1 upregulation was revealed to drive gastric cancer progression by targeting miR-376b-3p (29). Additionally, TTN-AS1 was reported to promote the proliferation of esophageal squamous cell carcinoma, cervical cancer and papillary thyroid cancer (18,19,30).…”

lncRNA TTN‐AS1 facilitates proliferation, invasion, and epithelial‐mesenchymal transition of breast cancer cells by regulating miR‐139‐5p/ZEB1 axis

“…19,20 For example, TTN-AS1 has been identified as a novel lncRNA with previously published studies suggesting that TTN-AS1 is an oncogene in multiple cancers, for instance, hepatocellular carcinoma, cervical cancer, papillary thyroid cancer, and gastric cancer. 21,22 Cui et al 23 established that TTN-AS1 drives papillary thyroid carcinoma progression by regulation of the microRNA (miRNA)-153-3p/ZNRF2 axis and activation of the PI3K/Akt/mTOR pathway. Lin et al 24 demonstrated that TTN-AS1 was able to drive esophageal squamous cell carcinoma cell proliferation and invasionmetastasis, and induce competitive binding of miRNA-133b, resulting in the upregulation of Snail1, HuR, and FSCN1.…”