MiR-146b-5p functions as a suppressor miRNA and prognosis predictor in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. However, science has not yet been able to substantially improve the prognosis of lung cancer patients. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor development and metastasis. Expression of six miRNAs previously shown to play roles in tumor development (miR-146b-5p, miR-128b, miR-21, miR-221, miR-34a, and Let-7a) in other tumor types was examined using real-time RT-PCR in 78 specimens of NSCLC. The results revealed that patients with low expression of miR-146b-5p had significant shorter median and mean survival time than those with high miR-146b-5p expression (33.00 and 30.44 months versus 42.0 and 36.90 months, respectively; log-rank test P=0.048), thus low miR-146b-5p expression level was associated with poor prognosis in NSCLC patients. Univariate Cox hazard regression analysis demonstrated that miR-146b-5p expression levels tended to be a significant prognostic indicator of NSCLC (adjusted hazard ratio=0.482, 95% CI: 1.409- 29.593, P=0.016). Multivariate Cox proportional hazard regression analysis showed that miR-146b-5p expression levels were an independent prognostic factor for NSCLC patients (hazard ratio=0.259, 95% CI: 0.083-0.809, P=0.020). Furthermore, the effects of miR-146b-5p and miR-146b-3p on NSCLC cell growth and invasion in vitro were investigated. Our findings demonstrate that ectopic expression of miR-146b-5p suppressed cell proliferation, clonogenicity, migration/ invasion and also induced G1 arrest in vitro, but did not induce cell apoptosis; whereas enforced expression of miR-146b-3p did not have a significant effect on cell growth and metastasis. Further experiments indicated that miR-146b-5p could reduce mRNA levels of MMP16 and TRAF6 in vitro and was negatively related to the expression of TRAF6 in human NSCLC tissues. In a mouse model, Ago-miR-146b-5p could significantly inhibit the growth of lung cancer xenografts in nude mice. In conclusion, our findings demonstrate that miR-146b-5p functions as a suppressor miRNA and prognosis predictor in NSCLC.

Inhibition of miR146b‐5p suppresses CT‐guided renal cell carcinoma by targeting TRAF6

“…In this study, we identified TRAF6 as the target of miR146b‐5p in mediating the effects of miR146b‐5p on tumor growth. Our results are consistent with previous reports showing that miR146‐5p targets TRAF6 to regulate relevant cellular functions . It is interesting that miR146‐5p is able to both suppress and promote tumor growth by targeting the same molecular.…”

“…Our results are consistent with previous reports showing that miR146-5p targets TRAF6 to regulate relevant cellular functions. 11,13,16 It is interesting that miR146-5p is able to both suppress and promote tumor growth by targeting the same molecular. In fact, in our study, we also found that TRAF6 knock out mice showed suppressed orthotopic tumor growth to the same extent as treatment of miR146-5p inhibitor in wild type mice.…”

“…Quantitative real time‐reverse transcription polymerase chain reaction (qRT‐PCR) was performed to measure the miR146b‐5p expression and mRNA levels of relevant genes as described previously . Briefly, total RNA was isolated using TRIzol ® RNA Isolation Reagents.…”

“…Quantitative real time-reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure the miR146b-5p expression and mRNA levels of relevant genes as described previously. 11 Briefly, total RNA was isolated using TRIzol ® RNA Isolation Reagents. An equivalent amount of RNA from each sample was used as a template to make cDNA using the TaqMan MiRNA reverse transcription kit (Applied Biosystems, Waltham, MA) for miR146-5p and the M-MLV Reverse Transcriptase kit (Promega, Madison, WI) for other genes.…”

Loss of miR‐146b‐5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL‐17A pathway

“…31 To explore the differential expression of miRNAs in T-ALL, we chose the GSE51908 dataset, which is the largest T-ALL patient cohort for bioinformatics analysis, 24 but, to date, the standard for screening differentially expressed genes is still not uniform. Multiple groups reported that miR-146b-5p is downregulated in breast cancer, 34 prostate cancer, 35 hepatocellular carcinoma, 36 non-small-cell lung cancer 37 and so on. In this study, we adopted a stringent Currently, some labs are focusing on miR-146b-5p expression and function in various cancers.…”