Novel MicroRNA signatures in HPV-mediated cervical carcinogenesis in Indian women.
This study aimed to investigate the role of miRNAs in HPV-mediated cervical pre-cancer and cancer cases in Indian population. We analysed the HPV infection and its genotypes in uterine cervical pre-cancer (n = 80), cancer (n = 200) and normal cervical samples (n = 150) by consensus sequence PCR followed by type specific PCRs. Also, microRNA profiling was done in a subset of cervical pre-cancer (n = 20), cancer cases (n = 50) and normal samples (n = 30) by real-time quantitative PCR (qRT-PCR). The prevalence of HPV infection in pre-cancer was found to be 81 % (65/80) and 94 % (188/200) in cancer cases, with most predominant high-risk HPV type-16 (HR-HPV-16) in 83 % of cancer and 91 % of pre- cancer cases, respectively. Whereas in controls, the HPV infection was found to be very low (5 %). The miRNA profiling revealed that in cervical pre-cancer, 100 miRNAs were significantly (p < 0.001) differentially expressed with 70 miRNAs upregulated and 30 miRNAs downregulated. In cervical cancer cases, 383 miRNA were found to be differentially expressed (p < 0.001), of which 350 miRNAs were upregulated and 33 miRNAs were downregulated. We also observed that 182 miRNAs were differentially expressed (p < 0.001) in HPV-16/18-positive (SiHa/HeLa) cell lines compared with HPV-negative (C33A) cell line. In addition, we identified the novel microRNAs such as miR-892b, miR-500, miR-888, miR-505 and miR-711 in cervical precancerous lesions and cervical cancer cases in Indian population. Taken together, the study demonstrates a crucial role of microRNAs in cervical cancer, which may serve as potential early diagnostic markers for cervical carcinogenesis.
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India.|Department of Microbiology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India.
Shweta
S
Sharma
Division of Molecular Oncology, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India.
Showket
S
Hussain
Institute of Genomics and Integrated Biology, Mall Road, New Delhi, India.
Kartik
K
Soni
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India.
Pallavi
P
Singhal
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India.
Richa
R
Tripathi
Department of Microbiology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India.
V G
VG
Ramachandran
Department of Pathology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India.
Sonal
S
Sharma
Department of Microbiology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India.
Shukla
S
Das
Institute of Genomics and Integrated Biology, Mall Road, New Delhi, India.
Beena
B
Pillai
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India. mausumi.bharadwaj@gmail.com.
Mausumi
M
Bharadwaj
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D059467:Transcriptome; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000821:virology
D014408:Biomarkers, Tumor; D035683:MicroRNAs
Cervical cancer; HPV; MicroRNAs