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Expression of mitochondrial genes MT-ND1, MT-ND6, MT-CYB, MT-COI, MT-ATP6, and 12S/MT-RNR1 in colorectal adenopolyps

Tumor Biology

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Abstract

Despite improvements in treatment strategies, colorectal cancer (CRC) still has high mortality rates. Most CRCs develop from adenopolyps via the adenoma-carcinoma sequence. A mechanism for inhibition of this sequence in individuals with a high risk of developing CRC is urgently needed. Differential studies of mitochondrial (mt) gene expressions in the progressive stages of CRC with villous architecture are warranted to reveal early risk assessments and new targets for chemoprevention of the disease. In the present study, reverse transcription-quantitative PCR (RT-qPCR) was used to determine the relative amount of the transcripts of six mt genes [MT-RNR1, MT-ND1, MT-COI, MT-ATP6, MT-ND6, and MT-CYB (region 648–15887)] which are involved in the normal metabolism of mitochondria. A total of 42 pairs of tissue samples obtained from colorectal adenopolyps, adenocarcinomas, and their corresponding adjacent normal tissues were examined. Additionally, electron transport chain (ETC), complexes I (NADH: ubiquinone oxidoreductase) and III (CoQH2-cytochrome C reductase), and carbonyl protein group contents were analyzed. Results indicate that there were differential expressions of the six mt genes and elevated carbonyl protein contents among the colorectal adenopolyps compared to their paired adjacent normal tissues (p < 0.05). The levels of complexes I and III were higher in tumor tissues relative to adjacent normal tissues. Noticeably, the expression of MT-COI was overexpressed in late colorectal carcinomas among all studied transcripts. Our data suggest that increased expressions in certain mt genes and elevated levels of ROS may potentially play a critical role in the colorectal tumors evolving from adenopolyps to malignant lesions.

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Abbreviations

12S/MT-RNR1 :

Mitochondrial encoded 12S ribosomal RNA

ATCB :

Beta actin

CA :

Adenocarcinoma

Cp :

Crossing point

CRC :

Colorectal cancer

DNPH :

2,4-Dinitrophenylhydrazine

ETC :

Electron transport chain

FAP :

Familial adenomatous polyposis

GAPDH :

Glyceraldehyde 3 phosphate dehydrogenase

HILF1α :

Hypoxia inducible factor 1-alpha

MT :

Mitochondrial

MT-ATP6 :

ATP synthase F0 subunit 6

MT-COI :

Mitochondrial encoded cytochrome oxidase I

MT-CYB :

Mitochondrial encoded cytochrome b

MT-DNA :

Mitochondria DNA

MT-ND1 :

Mitochondrial encoded NADH dehydrogenase 1

MT-ND6 :

Mitochondrial encoded NADH dehydrogenase 6

ROS :

Reactive oxygen species

RT-qPCR :

Reverse transcription quantitative polymerase chain reaction

TA :

Tubular adenoma

TV :

Tubulovillous

UBC :

Ubiquitin

V :

Villous adenoma

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Acknowledgments

We acknowledge the RCMI G12 MBRC Program from the National Institute of Minority Health and Health Disparities, Grant Number 8G12MD007602. To those investigators whose meritorious works could not be cited due to space limitations, we honestly apologize. This work was supported by grant NIH-NIGMS GM099663 awarded to Dr. Felix O Aikhionbare. We would also like to acknowledge William Roth and Saravanakumar Muthusamy for their technical and editing support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH-NIMHD and NIGMS.

Author contributions

Conception and design: L. Wallace, F.O. Aikhionbare, and S. Mehrabi; development of methodology: L. Wallace, S. Mehrabi, and F.O. Aikhionbare; acquisition of data: L. Wallace, S. Mehrabi, and M. Bacanamwo; analysis and interpretation of data: L. Wallace, S. Mehrabi, X. Yao, and F.O. Aikhionbare; writing: L. Wallace, S. Mehrabi, and F.O. Aikhionbare.

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Authors and Affiliations

  1. Department of Medicine, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30310, USA

    LaShanale Wallace, Sharifeh Mehrabi & Felix O. Aikhionbare

  2. Department of Physiology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA, 30310, USA

    Methode Bacanamwo & Xuebiao Yao

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  1. LaShanale Wallace
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  2. Sharifeh Mehrabi
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Correspondence to Felix O. Aikhionbare.

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Wallace, L., Mehrabi, S., Bacanamwo, M. et al. Expression of mitochondrial genes MT-ND1, MT-ND6, MT-CYB, MT-COI, MT-ATP6, and 12S/MT-RNR1 in colorectal adenopolyps. Tumor Biol. 37, 12465–12475 (2016). https://doi.org/10.1007/s13277-016-5101-3

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