Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer.
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.
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [3] Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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He
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Wang
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Zhang
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Huang
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Li
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Xiong
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Zhang
State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Jia
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Pathology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Yun
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Pathology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Luo
1] State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China [2] Department of Gynecology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.
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Zheng
D000328:Adult; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016000:Cluster Analysis; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases