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Tumor Biology

, Volume 37, Issue 8, pp 10357–10364 | Cite as

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

  • Suresh Govatati
  • Sravanthi Malempati
  • Bulle Saradamma
  • Dasi Divyamaanasa
  • B. Prathap Naidu
  • Pallaval Veera Bramhachari
  • Nagesh Narayana
  • Sisinthy Shivaji
  • Manjula Bhanoori
  • Raghava Rao Tamanam
  • Pasupuleti Sreenivasa Rao
  • Varadacharyulu Nallanchakravarthula
Original Article

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) [310C’ 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.

Keywords

Colorectal cancer Mitochondria D-loop Mn-SOD Polymorphism 

Notes

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)].

Supplementary material

13277_2016_4918_MOESM1_ESM.doc (30 kb)
Online Resource ESM 1 (DOC 30 kb)
13277_2016_4918_MOESM2_ESM.doc (110 kb)
Online Resource ESM 2 (DOC 110 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Suresh Govatati
    • 1
  • Sravanthi Malempati
    • 2
  • Bulle Saradamma
    • 1
  • Dasi Divyamaanasa
    • 3
  • B. Prathap Naidu
    • 4
  • Pallaval Veera Bramhachari
    • 4
  • Nagesh Narayana
    • 5
  • Sisinthy Shivaji
    • 5
    • 6
  • Manjula Bhanoori
    • 7
  • Raghava Rao Tamanam
    • 8
  • Pasupuleti Sreenivasa Rao
    • 9
  • Varadacharyulu Nallanchakravarthula
    • 1
  1. 1.Department of BiochemistrySri Krishnadevaraya UniversityAnantapurIndia
  2. 2.Department of Biochemistry, Dr. MRAR PG CenterKrishna UniversityNuzvidIndia
  3. 3.Gandhi Institute of Technology and Management Dental CollegeVisakhapatnamIndia
  4. 4.Department of BiotechnologyKrishna UniversityMachilipatnamIndia
  5. 5.CSIR-Centre for Cellular and Molecular BiologyHyderabadIndia
  6. 6.Presently at: Jhaveri Microbiology CentreL V Prasad Eye InstituteHyderabadIndia
  7. 7.Department of BiochemistryOsmania UniversityHyderabadIndia
  8. 8.Department of BiochemistryAndhra UniversityVisakhapatnamIndia
  9. 9.Department of Advanced Research CentreNarayana Medical College and HospitalsNelloreIndia

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