ABSTRACT
Colorectal tumors are mostly of epithelial origin and represent a wide spectrum of neoplasms. About 97% of colorectal cancer originating from benign lesions of adenomatous polyps are adenocarcinomas. Reactive oxygen species (ROS) generating from mitochondrial DNA (mtDNA) mutations and microRNAs (miRNAs) are associated with oncogene and tumor suppressor genes regulation which are known to parallel the tissue abnormalities involved with tumorigenesis such as colorectal adenoma to adenocarcinoma. However, the differential expression patterns of mitochondrial associated microRNAs (referred as MitomiRs) among colorectal adenomatous polyps progression is yet to be determined. Thus, the aim of this study was to determine the differential expressions profiles of MitomiRs (miR-24, miR-181, miR-210, miR-21 and miR378) in patients with colorectal adenomatous polyps tissues in correlation with clinicopathological tumor architectures of tubular, tubulovillous, villous adenomas and adenocarcinomas. Isolation of mitochondria RNA from colorectal adenomatous polyps, adenocarcinomas, and normal adjacent tissue samples was performed and assessed for mitochondrial associated miRNAs expression differences using quantitative reverse transcription PCR. Data from this study demonstrates that mitochondria genome expression of mitomiRNAs; miR-24, miR-181, miR-210, miR-21 and miR-378 in colorectal tissue samples varies among the adenomatous polyps. Expression of mitomiRNAs 24, 181, 210 and 378 progressively increased from the precancerous of adenomatous polyps to adenocarcinoma. In addition, miR-210 and miR-181 expression increased 3 folds in villous adenomas and greater than 3 folds increased in miR378 in adenocarcinoma (p < 0.005) when compared to tubular adenoma. Meanwhile, miR-21 increased progressively in adenoma tissues but decreased almost 2.5 folds in adenocarcinomas when compared to villous adenoma tissues (p < 0.001). These results suggest mitomiRs may regulate important mitochondrial functional pathways leading to a more favorable environment for transformation or progression of colorectal adenomatous polyps into adenocarcinomas.
ABSTRACT
BACKGROUND: Aldosterone, one of the major culprits associated with the renin-angiotensin-aldosterone system (RAAS), is significantly elevated following high salt administration in Dahl rats. Since we have previously demonstrated that aldosterone (ALDO) upregulates cyclooxygenase (COX) expression in the kidney, the present study was design to assess whether prostaglandin release is involved in the effects of chronic aldosterone treatment on vascular function of the aorta from nonhypertensive Dahl salt-sensitive rats. FINDINGS: The effects of aldosterone on arachidonic acid metabolism and on the expression of cyclooxygenase (COX)-2 were evaluated in the Dahl salt sensitive (DS) rat aorta, renal, femoral and carotid arteries. DS rats on a low salt (0.3% NaCl) diet were treated with or without ALDO for four weeks. Indirect blood pressure (BP), the release of prostacyclin (PGI2) and prostaglandin E2, and the expression of COX-2 were measured to assess the vascular remodelling by aldosterone. Vascular function was also assessed by contractile responsiveness in the aorta to phenylephrine. ALDO increased BP (17 ± 1%) and inhibited the basal release of PGE2. ALDO enhanced vascular reactivity to phenylephrine and up regulated the expression of COX-2 in both aorta and renal vessels but reduced COX-2 expression in the femoral artery. CONCLUSIONS: These data reveal that the effect of ALDO in the vasculature is tissue specific and may involve the inhibition of PGE2 release. Thus, suggesting a role for prostaglandins in the vasculopathic aspects of aldosterone.
