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Novel MicroRNA signatures in HPV-mediated cervical carcinogenesis in Indian women

Tumor Biology volume 37, pages 4585–4595 (2016)Cite this article

Abstract

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.

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Acknowledgments

This work was supported by the core funding of ICPO (ICMR) to MB. SS is grateful to the Indian Council of Medical Research (ICMR) for their Senior Research Fellowships. We would like to thank the patients and their family members too.

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Affiliations

  1. Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India

    Shweta Sharma, Pallavi Singhal, Richa Tripathi & Mausumi Bharadwaj

  2. Department of Microbiology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India

    Shweta Sharma, V. G. Ramachandran & Shukla Das

  3. Division of Molecular Oncology, Institute of Cytology & Preventive Oncology, I-7 Sector 39, Noida, 201301, India

    Showket Hussain

  4. Institute of Genomics and Integrated Biology, Mall Road, New Delhi, India

    Kartik Soni & Beena Pillai

  5. Department of Pathology, UCMS & GTB Hospital, Dilshad Garden, New Delhi, India

    Sonal Sharma

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  1. Shweta Sharma
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  2. Showket Hussain
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  3. Kartik Soni
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  4. Pallavi Singhal
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  6. V. G. Ramachandran
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  7. Sonal Sharma
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Correspondence to Mausumi Bharadwaj.

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Sharma, S., Hussain, S., Soni, K. et al. Novel MicroRNA signatures in HPV-mediated cervical carcinogenesis in Indian women. Tumor Biol. 37, 4585–4595 (2016). https://doi.org/10.1007/s13277-015-4248-7

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  • DOI: https://doi.org/10.1007/s13277-015-4248-7

Keywords

  • Cervical cancer
  • HPV
  • MicroRNAs