title: Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability.
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.
authors: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515 003, India.
authors: Suresh
authors: S
authors: Govatati
authors: Department of Biochemistry, Dr. MRAR PG Center, Krishna University, Nuzvid, India.
authors: Sravanthi
authors: S
authors: Malempati
authors: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515 003, India.
authors: Bulle
authors: B
authors: Saradamma
authors: Gandhi Institute of Technology and Management Dental College, Visakhapatnam, India.
authors: Dasi
authors: D
authors: Divyamaanasa
authors: Department of Biotechnology, Krishna University, Machilipatnam, India.
authors: B Prathap
authors: BP
authors: Naidu
authors: Department of Biotechnology, Krishna University, Machilipatnam, India.
authors: Pallaval Veera
authors: PV
authors: Bramhachari
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Nagesh
authors: N
authors: Narayana
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.|Presently at: Jhaveri Microbiology Centre, L V Prasad Eye Institute, Hyderabad, India.
authors: Sisinthy
authors: S
authors: Shivaji
authors: Department of Biochemistry, Osmania University, Hyderabad, India.
authors: Manjula
authors: M
authors: Bhanoori
authors: Department of Biochemistry, Andhra University, Visakhapatnam, India.
authors: Raghava Rao
authors: RR
authors: Tamanam
authors: Department of Advanced Research Centre, Narayana Medical College and Hospitals, Nellore, India.
authors: Pasupuleti Sreenivasa
authors: PS
authors: Rao
authors: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515 003, India. suresh.g1tpl@gmail.com.
authors: Varadacharyulu
authors: V
authors: Nallanchakravarthula
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis*
chemical_list: D004272:DNA, Mitochondrial; D013482:Superoxide Dismutase
keywords: Colorectal cancer; D-loop; Mitochondria; Mn-SOD; Polymorphism