miR‐194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts

Abstract

MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H O -induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

“…3B) showed that the uorescence intensities of Cy5 were obviously different in each cell line, indicating different miRNA-194 expression levels in the three cell lines. In agreement with previous reports, [36][37][38] Huh7 had a higher miRNA-194 expression level than HepG2, while HEK293 exhibited a quite low expression level, and quantitative reverse transcription PCR (qRT-PCR) was further used to conrm the relative miRNA-194 expression levels (Fig. S10 †).…”

Avenanthramide A Induces Cellular Senescence via miR-129-3p/Pirh2/p53 Signaling Pathway To Suppress Colon Cancer Growth

“…Cell senescence has been considered as an effective tumor-suppressor mechanism, which results in permanent cell cycle arrest . Although the factors that provoke tumor cell senescence remain unclear, many studies have demonstrated that miRNAs function as potential regulators of cellular senescence. , The expression of miR-129-3p is downregulated in various tumors, including endometrial, hepatic, gastrointestinal, and colon cancer. Evidence from the previous literature suggests that miR-129-3p serves as a tumor suppressor and is closely related to the activation of apoptotic cell death, autophagy, cell cycle arrest, and sensitization of CRC cells to chemotherapy. , Notably, our findings are in agreement with the previous data demonstrating that miR-129-3p directly targets IGF2BP3 and MAPK1 to arrest G1/S transition .…”

“…MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs, as silencers of various target genes through translational repression or mRNA degradation, and play a critical role in regulating numerous biological processes, including carcinogenesis . Growing evidence suggests that miRNAs could serve as unique proto-oncogene or tumor suppressors that regulate cellular senescence and its dysregulation leads to initiation and development of cancer. , Moreover, it has been reported that miR-129-3p is downregulated in multiple cancer types, where it functions as a tumor suppressor. , However, the role of miR-129-3p in cellular senescence remains ambiguous.…”

The p53/miRNAs/Ccna2 pathway serves as a novel regulator of cellular senescence: Complement of the canonical p53/p21 pathway

“…Previous studies have identified various p53 responsive miRNAs, including miR‐34a, miR‐29a/b/c, miR‐124, miR‐199a, and miR‐194 (Jeong et al, ; Liao et al, ). Among these miRNAs, miR‐34a and miR‐29 have been demonstrated to be typical Aging‐related miRNAs (Boon et al, ; Hu et al, ); in addition, miR‐194 was closely associated with cellular senescence as well (Xu et al, ). Though miR‐124 has been reported to be associated with several Aging‐related disease, including Alzheimer's disease and Parkinson's disease (Fang et al, ; Wang, Ye et al, ), the effect and underlying mechanism of miR‐124 on Aging process were largely unknown.…”