miR-195-5p regulates cell proliferation, apoptosis, and invasion of thyroid cancer by targeting telomerase reverse transcriptase

Abstract

In most human primary cancers, the expression, or telomerase activity, of telomerase reverse transcriptase (TERT) is detectable. However, the mechanism ofTERTactivity within oncogenesis of thyroid cancer remains largely unknown. In this study, we identified miR-195-5p as having involvement in cell proliferation, apoptosis, and invasion in human thyroid cancer. MTT was used to measure cell proliferation, Transwell chamber was used to measure invasion. Western blotting was used to detect the expressions of TERT, PCNA, and Ki67. Target gene prediction software predicted that TERT may be the target gene of miR-195-5p. Luciferase reporting system was used to identify the targeting relationship. A significant increase of in TERT expression was observed by immunohistochemistry compared with normal tissue, however, a decrease in miR-195-5p expression using qRT-PCRand western blot compared with normal cells. Functional analysis demonstrates that miR-195-5p negatively correlated withTERTand inhibitedTERTexpression through its interaction with theTERT3ʹ-untranslatedregion (3ʹ-UTR). Overexpression of miR-195-5p was shown to inhibit proliferation and invasion, and promote apoptosis of CAL-62 thyroid cancer cells. miR-195-5p-mediatedeffects were rescued by the overexpression ofTERT. Altogether, our data demonstrate that miR-195-5p regulates cell proliferation, apoptosis, and invasion in human thyroid cancer viaTERT, providing evidence of a new potential therapeutic target for further investigation.

Integrated Analysis of Altered lncRNA, circRNA, microRNA, and mRNA Expression in Hepatocellular Carcinoma Carrying TERT Promoter Mutations

“… 32 Additionally, it has been reported that ncRNA can regulate TERT expression in cancer; however, it is still unclear whether TERT promoter mutations can influence ncRNA regulation. 29 The evidence indicates that ncRNA might be a novel prospect of TERT promoter mutation research in HCC. Since TERT promoter mutations are located in the noncoding part, relative sequencing data are lacking in previous studies.…”

“…It has been reported that hsa-miR-195-5p works as a tumor suppressor in thyroid cancer by targeting TERT mRNA. 29 On the other hand, many studies failed to observe significant correlations between TERT promoter mutations and increased TERT expression. [12][13][14] It has been reported that the increase in TERT expression is not significant in HCC samples with TERT promoter mutations.…”

The effect and mechanism of miR-30e-5p targeting SNAI1 to regulate epithelial-mesenchymal transition on pancreatic cancer

“…Annexin V-FITC and Propidium Iodide were mixed into cells and incubated in the dark for 15 minutes. Finally, flow cytometry was used to detect cell apoptosis [ 25 ].…”

TERT Promoter Mutated Follicular Thyroid Carcinomas Exhibit a Distinct microRNA Expressional Profile with Potential Implications for Tumor Progression

“…1 B-C). Interestingly, hsa-miR-195-5p has been endowed with putative tumor suppressor functions in thyroid cancer, as it inhibits cell proliferation and invasion in thyroid cancer cell lines, while promoting apoptosis [ 8 ]. The most up-regulated miRNA in the TERT promoter mutated FTCs, hsa-miR-200b-3p, has been shown to be down-regulated in anaplastic thyroid carcinoma (ATC)—but little is known regarding the roles of this miRNA in WDTCs [ 9 ].…”

“…In this pilot series, we demonstrate that TERT promoter mutated FTCs carry a unique miRNA signature and highlight a number of interesting candidates for future studies in terms of disease progression and prognosis. The observed down-regulation of hsa-miR-195-5p should be of particular interest for future studies, as this miRNA could constitute a potent tumor suppressor in thyroid cancer cell lines by targeting TERT mRNA [ 8 ]. Moreover, cancer-related mRNA targets of the differentially expressed miRNAs were amassed in cell cycle and P53 signaling, providing a possible link between TERT promoter mutations and dysregulation of these pathways in FTCs.…”