MicroRNAs have been implicated in regulating diverse cellular pathways. Emerging evidence indicates that miR-143 plays causal roles in cancer tumorigenesis as a tumor suppress gene; however, its role in prostate cancer tumorigenesis remains largely unknown. The aims of this study were to verify the effect of miR-143 on proliferation and migration abilities of prostate cancer cells. The expression level of miR-143 and its target gene KRAS were measured by realtime PCR and western blotting, respectively. Effects of miR-143 in cell proliferation, migration and chemosensitivity were evaluated by MTT assay, FACS cell cycle analysis, colony formation assay, and transwell migratory assay. Our results revealed an inverse correlation of expression between miR-143 and KRAS protein in prostate cancer samples (Pearson's correlation scatter plots: R = -0.707, P < 0.05). Moreover, over-expression of miR-143 in prostate cancer cells suppressed their proliferation and migration and increased their sensitivity to docetaxel by targeting EGFR/RAS/MAPK pathway. These findings suggest that miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing KRAS and subsequent inactivation of MAPK pathway, which provides a potential development of a new approach for the treatment of prostate cancer.

Our findings suggest that ubiquitous loss of miR-146a is a critical mechanism for overexpression of EGFR in CRPC, which is crucial to better understanding the pathogenesis of CRPC.

BackgroundAbnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected.Methodology/Principal FindingsUsing the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538–1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia.ConclusionsHypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation.

miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment.

Summary Several molecular epidemiological studies have been conducted to examine the association between MTHFR C677T polymorphism and male infertility susceptibility, but the results remain inconsistent. To derive a more precise estimation of the relationship, a meta‐analysis was performed. A total of 10 case–control studies, including 2275 cases and 1958 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals were used to assess the strength of association in the additive model, dominant model and recessive model. In the overall analysis, no significant association between the polymorphism and risk of male infertility was observed. Stratified analysis showed that significantly strong association between MTHFR C677T polymorphism and male infertility were present only in Asians (OR = 1.79 for TT vs. CC genotype; OR = 1.42 for CT/TT vs. CC genotype; OR = 1.50 for TT vs. CC/CT genotype; OR = 1.36 for T vs. C allele), but not in Caucasians. Additionally, MTHFR 677T was associated with a significant increase in the risk of azoospermia in all genetic models. No significantly increased risks of oligoasthenoteratozoospermia were found in any of the genetic models. In conclusion, this meta‐analysis supports that MTHFR C677T polymorphism is capable of causing male infertility susceptibility in Asians, but not in Caucasians.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

Bladder cancer is the second most common urological malignancy in the US and is the most frequently diagnosed urological malignancy in China. An increasing amount of evidence indicates that microRNAs perform extremely important functions in many biological processes related to the formation and progression of cancers, including bladder cancer. Previous studies have reported that microRNA‑379-5p (miR-379-5p) is involved in tumour initiation and development in human cancers. However, the expression pattern, biological functions and the underlying mechanisms of miR-379-5p in bladder cancer remain unknown. The present study demonstrated that the expression levels of miR‑379-5p in bladder cancer tissues and cell lines were lower than the levels in adjacent normal tissues and the human bladder epithelial immortalized SV-HUC-1 cell line. Restoration of the expression of miR-379-5p inhibited bladder cancer cell proliferation, migration and invasion. Mouse double minute 2 (MDM2) was identified as a direct target gene of miR-379-5p. Furthermore, similar to miR-379-5p overexpression in bladder cancer cells, inhibition of MDM2 exerted tumor-suppressive effects. Rescue experiments showed that upregulation of MDM2 reversed the inhibitory effects of miR-379-5p on bladder cancer cell proliferation, migration and invasion. MDM2 was highly expressed and inversely correlated with miR-379-5p expression in bladder cancer tissues. These findings suggest that the miR-379-5p/MDM2 pathway plays an important role in bladder cancer and could serve as a potential candidate for bladder cancer therapeutics.

No abstract