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Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability

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Tumor Biology

Abstract

Mitochondrial displacement loop (D-loop) is a hot spot for mitochondrial DNA (mtDNA) alterations that effects cellular reactive oxygen species (ROS) generation. Manganese-superoxide dismutase (Mn-SOD) is a major antioxidant enzyme that protects cells from ROS-mediated damage. In the present study, we investigated the relationship between sequence alterations of mitochondrial D-loop and Mn-SOD expression in colorectal cancer (CRC). Genotyping of entire mitochondrial D-loop (1124 bp) was carried out on mtDNA of analogous tumor and normal tissues from 35 CRC patients of south Indian origin by PCR-sequencing analysis. Tumor-specific large-scale mtDNA deletions and Mn-SOD expression was analyzed by PCR and Western blot analysis, respectively. We identified 87 polymorphisms in the D-loop region of tumor and/or control tissues. Polymorphisms were predominantly located in hypervariable region I (67.9 %) than in II (32.1 %) of D-loop. Significantly increased mtDNA microsatellite instability (mtMSI) [310‘C’ insertion (P = 0.00001) and T16189C (P = 0.0007)] and elevated Mn-SOD expression was observed in tumor tissues compared with controls. Interestingly, mtMSI was significantly high in tumors with Mn-SOD overexpression. Tumor-specific large-scale mtDNA deletions were not observed in CRC tissues. In conclusion, mtMSI and Mn-SOD overexpression are a common event in CRC. The analysis of mtMSI and/or Mn-SOD expression might help to identify patients at high risk for disease outcome, thereby helping to refine therapeutic decisions in CRC.

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Acknowledgments

We deeply thank all the medical staff and study subjects involved in this study. Dr. Suresh Govatati acknowledges the financial support from the University Grants Commission, New Delhi, under its Dr. D.S. Kothari postdoctoral scheme [No.F.4-2/2006 (BSR)/13-1014/2013 (BSR)].

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Authors and Affiliations

  1. Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515 003, India

    Suresh Govatati, Bulle Saradamma & Varadacharyulu Nallanchakravarthula

  2. Department of Biochemistry, Dr. MRAR PG Center, Krishna University, Nuzvid, India

    Sravanthi Malempati

  3. Gandhi Institute of Technology and Management Dental College, Visakhapatnam, India

    Dasi Divyamaanasa

  4. Department of Biotechnology, Krishna University, Machilipatnam, India

    B. Prathap Naidu & Pallaval Veera Bramhachari

  5. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

    Nagesh Narayana & Sisinthy Shivaji

  6. Presently at: Jhaveri Microbiology Centre, L V Prasad Eye Institute, Hyderabad, India

    Sisinthy Shivaji

  7. Department of Biochemistry, Osmania University, Hyderabad, India

    Manjula Bhanoori

  8. Department of Biochemistry, Andhra University, Visakhapatnam, India

    Raghava Rao Tamanam

  9. Department of Advanced Research Centre, Narayana Medical College and Hospitals, Nellore, India

    Pasupuleti Sreenivasa Rao

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  1. Suresh Govatati
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Correspondence to Varadacharyulu Nallanchakravarthula.

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Govatati, S., Malempati, S., Saradamma, B. et al. Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability. Tumor Biol. 37, 10357–10364 (2016). https://doi.org/10.1007/s13277-016-4918-0

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