A Functional Polymorphism in the Promoter of MiR-143/145 Is Associated With the Risk of Cervical Squamous Cell Carcinoma in Chinese Women

Abstract

MiR-143/145 is down-regulated in cervical cancer, which may serve as a tumor suppressor by targeting KRAS and Ras-responsive element-binding protein (RREB1). Activated KRAS leads to down-regulation of miR-143/145 transcription in a RREB1-dependent manner, establishing a miR-143/145-KRAS-RREB1 feedback loop. A polymorphism rs4705343C/T in the promoter of miR-143/145 might influence the binding of TATA-binding protein. We hypothesized that the miR-143/145 rs4705343 and KRAS rs712 may be related to the occurrence of cervical squamous cell carcinoma (CSCC). In this study, we genotyped the 2 polymorphisms in 415 patients with CSCC and 504 controls using polymerase chain reaction–restriction fragment length polymorphism. The promoter activities were measured by the Dual-Luciferase Reporter Assay System. We found that the rs4705343TC genotype was associated with an increased risk of CSCC (adjusted odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.05–1.80). The significantly increased association was also observed in a dominant genetic model (adjusted OR = 1.32; 95% CI, 1.01–1.72). Combined analysis showed that individuals carrying the genotypes of rs4705343 TC/CC and rs712GT/TT had a 1.47-fold increased risk of CSCC (adjusted OR = 1.47; 95% CI, 1.01–2.15). By using multifactor dimensionality reduction software method, we identified a significant interaction between the miR-143/145 rs4705343 and KRAS rs712. Dual-Luciferase Reporter Assay showed that the luciferase activity was significantly lower in cells transfected with the rs4705343C allele than that of the rs4705343T allele. These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of CSCC in Chinese women.

The Microrna-143/145 Cluster in Tumors: A Matter of Where and When

“…The rs353292 variant, which displays reduced transcriptional activity in a Luciferase reporter assay [65], was shown to correlate with lower miR-143, but not miR-145, expression levels and CRC development in tumor samples. Similar findings were reported in the context of the rs4705342T > C and the rs4705343T > C variants, with the T alleles displaying reduced promoter activity and increased prostate cancer or cervical squamous cell carcinoma development [66,67]. A few SNPs correlating with reduced transcription and lower cancer risk have also been described, as in the case of the rs353293 allele in the cluster's promoter, which dictates lower transcriptional activity of a luciferase reporter and was a protective genetic marker in bladder cancer [68].…”

Association between functional polymorphisms in the promoter of the miR-143/145 cluster and risk of intracranial aneurysm

“…The primers, probes and enzymes used were processed as described previously1819. For internal quality control, about 5% samples were selected for Sanger sequencing, and the concordance rates among these quality control samples were found to be 100% between the assays.…”

“…The rs4705342 risk-associated T allele, located 510 bp upstream from the transcription start site, increases protein-binding affinity and decreases promoter activity18. On the other hand, the rs4705343 risk-associated C allele, located 400 bp upstream from the transcription start site, reduces luciferase activity19. These two SNPs were reported to be associated with the risk of essential hypertension, prostate cancer and cervical squamous cell carcinoma181920.…”

“…On the other hand, the rs4705343 risk-associated C allele, located 400 bp upstream from the transcription start site, reduces luciferase activity19. These two SNPs were reported to be associated with the risk of essential hypertension, prostate cancer and cervical squamous cell carcinoma181920. No study, to date, has investigated the association between these two polymorphisms and IA risk.…”

Current Concepts and Evaluation of Uro-Rectal Diseases by Transrectal Ultrasound: A Review

“…Prostate Cancer [107] Perianal Paget's Disease [108] Myxoid Liposarcoma [109] Malignant Fibrous Histiocytoma [110] Hemangiopericytoma [111] Cauda Equina Syndrome [112] Carcinoma of the Cervix [113] Carcinoma of the Vagina [114] Epidermoid Cysts [115] Prader-Willi Syndrome [116] Colorectal Carcinoma [117] Benign Prostate Hyperplasia [118] Microglandular Hyperplasia [119] Adenocarcinoma of Cervix [120] Adenoma Malignum [121] Adenosquamous Carcinoma of Cervix [122] Glassy Cell Carcinoma of Cervix [123] Adenoid Basal Carcinoma of Cervix [124] Adenomyosis [125] Uterine Fibroids [126] Endometrial Polyps [127] Hematoma [128] Fournier's Gangrene [129] Malakoplakia [130] Aneurysmal bone cyst [131] Ewing Sarcoma [132] Osteosarcoma [133] Chondrosarcoma [134] Neurofibroma [135] Neuroblastoma [136] Schwannoma [137] Chordoma [138] Malignant Schwannoma [139] Hemangioma [140] Myelolipoma [141] Leiomyoma [142] Villous Adenoma [143] Solitary Fibrous tumor [144] Castleman disease [145] Lymphoma [146] Gastrointestinal Stromal Tumor [147] Epithielial Malignancies …”