Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer

Abstract

Dicer is crucial for the maturation of microRNAs (miRNAs) and its dysregulation may contribute to tumor initiation and progression. The study explored the clinical implications of Dicer and its post-transcriptional regulation by microRNAs in cervical cancer. qRT-PCR and immunohistochemistry investigated Dicer mRNA and protein levels in cervical cancer tissues. The relationship between Dicer expression and survival was analyzed. MiRNA target prediction identified miRNAs that might target Dicer. Luciferase reporter and gain- or loss-of-function assays were performed. The results showed that 36.7% of cervical cancer cases showed low expression of Dicer mRNA and 63.3% cases showed high expression. At the protein level, 51% cases showed negative expression and 49% cases showed positive expression. Dicer mRNA and protein expressions were significantly associated with distant metastasis and recurrence in cervical cancer (P=0.002 and P=0.012, respectively). Multivariate Cox analysis indicated that low Dicer expression (P=0.016) and tumor stage (P=0.047) were independent predictors. Among the miRNAs predicted to target Dicer, 10 were detected by RT-PCR; their expressions were significantly higher in cervical cancers with lower Dicer expression than in those with higher Dicer expression and were negatively correlated with Dicer expression level (P<0.05). In vitro experiments demonstrated that miR-130a directly targeted Dicer mRNA to enhance migration and invasion in SiHa cells. Finally, survival analysis indicated that higher expression of miR-130a was significantly associated with poor disease-free survival. Taken together, Dicer expression regulated by miR-130a is an important potential prognostic factor in cervical cancer.

Association between the DICER rs1057035 Polymorphism and Cancer Risk: Evidence from a Meta-analysis of 1,2675 Individuals

“…DICER possesses a complex role in cancer through its ability to regulate the maturation of miRNA (Lyle et al, 2014). Growing research suggests that dysregulated expression of DICER might play a vital role in cancer risk and prognosis (Caffrey et al, 2013;Avery-Kiejda et al, 2014;He et al, 2014). Given the critical function of DICER in miRNA processing and the involvement of miRNAs in cancer development and progression, it is rational to speculate that host genomic polymorphism of DICER may influence the cancer risk.…”

Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients

“…miR-130a has been observed to play a critical role in various types of cancer. He et al (35) observed that miRNA-130a was upregulated in cervical cancer, which directly targeted Dicer mRNA, enhancing cellular growth, migration and invasion. In contrast, Li et al (36) detected that miR-130a was significantly downregulated in hepatocellular carcinoma.…”

Chicken gga-miR-130a targets HOXA3 and MDFIC and inhibits Marek’s disease lymphoma cell proliferation and migration

“…MiR-130a, miR-19, and miR-101 coregulat ATXN1 (ataxin 1) expression to modulate Spinocerebellar ataxia type 1 pathogenesis [68]. Additional studies revealed that miR-130a targets DICER1 (dicer 1, ribonuclease type III) in chronic lymphocytic leukemia [69] and cervical cancer [58]. In summary, miR-130a targets different genes associated with different diseases, emphasizing that the miRNA can bind to a number of diverse mRNAs.…”

“…Studies indicate that miR-130a is associated with lung cancer [50], gastric cancer [51,52], ovarian cancer [53][54][55][56][57], cervical cancer [58,59], and prostate cancer [60]. Recently, deep sequencing technology was used to identify differentially expressed host miRNAs in chickens [28,34,35,61,62].…”