miR-495 overexpression

In vivo, overexpressed miR-495 by injecting agomiR-495 led to a substantial decrease in the expression of mc1r and mitf in dorsal skin and liver, resulting in a reduction in skin melanin content, while the opposite results were obtained after miR-495 silencing by antagomiR-495. These findings suggest that miR-495 can target mc1r to regulate rainbow trout skin pigmentation, which provide a potential basis for using miRNAs as target drugs to treat pigmentation disorders and melanoma.

Overall, the results of the current study introduced miR-495-3p as a cell cycle progression suppressor, which may negatively regulate TGFβR1, TGFβR2, SMAD4, and BUB1 genes. This finding suggests miR-495-3p as a tumor suppressor candidate for further evaluation.

Overexpression of miR-495-3p impaired cell migration and invasion of PTC cells harboring the BRAFV600E mutation and affected the expression of targets predicted in the bioinformatic analysis, such as TGFB2, EREG and CCND1. Overall, our results indicate that the loss of miR-495-3p expression during PTC development might play an important role in its progression.

Conversely, our data showed that miR-495-3p overexpression hindered leukemic cell growth and TKI resistance even in Imatinib-resistant T315I-mutant cells as well as drug efflux activity through MDR1 regulation. To further investigate the role of miR-495-3p in CML patients, we found that predicted miR-495-3p targets were upregulated in patients in blast crisis involved in protein phosphorylation and associated with the worst prognosis. Taken together, our results demonstrate that down-regulation of miR-495-3p expression is important in the malignant phenotype of CML and TKI resistance mechanisms, which could be a useful biomarker and a potential therapeutic target to eradicate CML.

CREB1 regulates KPNA2 by inhibiting miR-495-3p transcription to control melanoma progression. Our results indicate the molecular mechanism by which the CREB1/miR-495-3p/KPNA2 axis regulates melanoma progression.

Overall, we showed that miR-495-3p reprograms sphingolipid rheostat towards ceramide by targeting Sphk1 and induces lethal mitophagy to suppress NSCLC tumorigenesis. The study identified a miR-mediated mechanism of sphingolipid reprogramming that could be beneficial in designing novel therapeutic strategies for NSCLC.

CircTMTC1 silence inhibited NPC growth and lung metastasis by targeting the miR-495-MET-eIF4G1 translational regulation axis in vivo. CircTMTC1 accelerates NPC progression through targeting miR-495 and consequently activating the MET-eIF4G1 translational regulation axis, suggesting potential therapeutic targets for NPC treatment.