Tumor Biology

, Volume 36, Issue 12, pp 9987–9994 | Cite as

HPV-type-specific response of cervical cancer cells to cisplatin after silencing replication licensing factor MCM4

  • Mitali Das
  • Shyam Babu Prasad
  • Suresh Singh Yadav
  • Arusha Modi
  • Sunita Singh
  • Satyajit Pradhan
  • Gopeshwar Narayan
Original Article


Minichoromosome maintenance (MCM) proteins play key role in cell cycle progression by licensing DNA replication only once per cell cycle. These proteins are found to be overexpressed in cervical cancer cells. In this study, we depleted MCM4, one of the MCM 2–7 complex components by RNA interference (RNAi) in four cervical cancer cell lines. The four cell lines were selected on the basis of their human papillomavirus (HPV) infection: HPV16-positive SiHa, HPV18-positive ME-180, HPV16- and HPV18-positive CaSki, and HPV-negative C-33A. The MCM4-deficient cells irrespective of their HPV status grow for several generations and maintain regular cell cycle. We did not find any evidence of augmented response to a short-term (48 h) cisplatin treatment in these MCM4-deficient cells. However, MCM4−/HPV16+ SiHa cells cannot withstand a prolonged treatment (up to 5 days) of even a sublethal dosage of cisplatin. They show increased chromosomal instability compared to their control counterparts. On the other hand, MCM4-deficient CaSki cells (both HPV16+ and 18+) remain resistant to a prolonged exposure to cisplatin. Our study indicates that cervical cancer cells may be using excess MCMs as a backup for replicative stress; however, its regulatory mechanism is dependent on the HPV status of the cells.


Cervical cancer HPV status MCM4 RNA interference Cisplatin Chromosomal instability 



The authors thankfully acknowledge the financial support from the Department of Biotechnology, Government of India (vide project no. BT/PR9246/Med/30/17/2007), to GN, SS, and SP; Banaras Hindu University (XIth Plan) to SS; Council of Scientific and Industrial Research, Government of India, for research fellowship to MD; and Interdisciplinary School of Life Sciences, Faculty of Science, Banaras Hindu University for equipment facilities.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Mitali Das
    • 1
  • Shyam Babu Prasad
    • 1
    • 4
  • Suresh Singh Yadav
    • 1
  • Arusha Modi
    • 1
  • Sunita Singh
    • 2
  • Satyajit Pradhan
    • 3
  • Gopeshwar Narayan
    • 1
  1. 1.Cancer Genetics Laboratory, Department of Molecular and Human GeneticsBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of Zoology, Mahila MahavidyalayaBanaras Hindu UniversityVaranasiIndia
  3. 3.Department of Radiotherapy and Radiation MedicineBanaras Hindu UniversityVaranasiIndia
  4. 4.Division of Molecular OncologyInstitute of Cytology and Preventive OncologyNoidaIndia

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