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Delineation of Mitochondrial Genome Expression in Colorectal Adenoma Progression
Başlık:
Delineation of Mitochondrial Genome Expression in Colorectal Adenoma Progression
Yazar:
Wallace, LaShanale, author.
ISBN:
9780355977066
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (83 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Felix O. Aikhionbare Committee members: Jason DeBruyne; Brandi Knight; Xuebiao Yao.
Özet:
Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the United States diagnosed in both men and women. Patients with colonic adenomatous polyps have a threefold higher risk of CRC over the general population. Moreover, a great deal of differences has been observed among patients with colonic adenomatous polyps during the course and outcome of the disease making application of appropriate therapies difficult. Given that CRC is considered an age related disease, the accumulation of reactive oxygen species (ROS) and oxidative DNA damage during the course of a lifetime may be deleterious leading to specific mitochondrial genome alterations involved in the development and progression of colorectal adenomatous polyps. Recent studies suggest the mitochondrion encodes miRNA sequences which may regulate different pathways involved in oxidative phosphorylation, apoptosis, and oxidative stress, all of which are pathways frequently deregulated in cancer. This study analyzed mitochondrial genome variations in 50 pairs of colorectal precancerous polyps (tubular, tubulovillous, villous) and adenocarcinoma tissues. Our hypothesis states that aberrant mitochondria genome expression contributes to the progression of colorectal adenomatous polyps to CRC. Variations within these different tissues were tested through the following experiments: (I) direct sequencing and high resolution restriction digestion to evaluate specific DNA variants (II) Gene expression analysis of mitochondrial encoded genes using reverse transcription quantitative PCR and (III) Pathway Studio and RT-qPCR analysis to determine MitomiRs expressed in colorectal polyp and carcinoma tissues. Three hundred and twenty seven mtDNA variants identified were predominately found in complexes IV and V of the electron transport chain. Additionally five mt-genes and one rRNA were differentially expressed among the colorectal adenopolyps compared to their paired adjacent normal tissue. Protein analysis results showed an increased expression of complexes I and III as well as elevated carbonyl content among the studied colorectal tumors. More importantly miRNAs 210 and 21 which target genes in these complexes significantly increased from early adenomas to late stage adenomas. These findings provide insight into the significant role the mitochondria plays during early progressive stages of CRC development. Therefore, further mitochondrial expression studies could render an alternate target for CRC biomarker discovery and novel therapeutics.
Notlar:
School code: 1943
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(680941.1) | 680941-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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