MiR-138-5p Suppresses Cell Growth and Migration in Melanoma by Targeting Telomerase Reverse Transcriptase

Abstract

Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene (hTERT), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of hTERT expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in hTERT regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower hTERT messenger RNA (mRNA) expression in human epidermal melanocytes, compared with melanoma cell lines (A2058, A375, SK-MEL-28) by quantitative polymerase chain reaction (qPCR) observing a negative correlation between them. A2058 melanoma cells were selected to be transfected with miR-138-5p mimic or inhibitor. Using luciferase assay, hTERT was identified as a direct target of this miRNA. Overexpression of miR-138-5p detected by Western blot revealed a decrease in hTERT protein expression (p = 0.012), and qPCR showed a reduction in telomerase activity (p < 0.001). Moreover, suppressions in cell growth (p = 0.035) and migration abilities (p = 0.015) were observed in A2058-transfected cells using thiazolyl blue tetrazolium bromide and flow cytometry, respectively. This study identifies miR-138-5p as a crucial tumor suppressor miRNA involved in telomerase regulation. Targeting it as a combination therapy with immunotherapy or targeted therapies could be used in advanced melanoma treatment; however, more preclinical studies are necessary.

Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1

“…Furthermore, previous studies demonstrated that miR-138-5p could inhibit the progression of cancers by suppressing the proliferation, growth, and migration of cancer cells, indicating that miR-138-5p may be a cancer-related miRNA. [21][22][23] Another study showed that circ_101238/miR-138-5p/CDK6 signaling axis could inhibit cell proliferation while promoting apoptosis of keloid fibroblasts. 24 Therefore, miR-138-5p may play a pivotal role in therapeutics for tumorous and fibrotic diseases, which still needs further exploration.…”

Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition

“…This result was in accordance with a previous study that showed a slowdown in wound healing by TAM in MCF-7 cells in a dose-dependent manner 81 . Moreover, it was previously reported that hTERT increases cell migration and its regulation with miR-138-5p suppresses cell growth and migration 82 – 84 .…”

Effect of icariin on the H2O2-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis

“…The reaction system was then subjected to a polymerase chain reaction PCR. Based on previous research, 24 to detect the levels of miR-138-5p, a TaqMan miRNA assay kit was used to detect (Applied Biosystems, Foster City, CA, USA). Using the 2 −∆∆ Ct technique.…”