Wallace LaShanale, Aikhionbare Karen, Banerjee Saswati, Peagler Katie, Pitts Mareena, Yao Xuebiao, Aikhionbare Felix
Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia, USA.
College of Science and Mathematics, Augusta University, Augusta, Georgia, USA.
Cancer Res J (N Y N Y). 2021 Mar;9(1):23-33. Epub 2021 Jan 25.
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 < 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 ( < 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.
结直肠肿瘤大多起源于上皮组织，涵盖了广泛的肿瘤类型。约97%源自腺瘤性息肉良性病变的结直肠癌为腺癌。由线粒体DNA（mtDNA）突变和微小RNA（miRNA）产生的活性氧（ROS）与癌基因和肿瘤抑制基因的调控相关，已知这些调控与肿瘤发生过程中涉及的组织异常情况平行，如结直肠腺瘤发展为腺癌。然而，线粒体相关微小RNA（称为MitomiRs）在结直肠腺瘤性息肉进展过程中的差异表达模式尚未确定。因此，本研究的目的是确定MitomiRs（miR - 24、miR - 181、miR - 210、miR - 21和miR378）在结直肠腺瘤性息肉患者组织中的差异表达谱，并与管状、管状绒毛状、绒毛状腺瘤及腺癌的临床病理肿瘤结构相关联。从结直肠腺瘤性息肉、腺癌及正常相邻组织样本中分离线粒体RNA，并使用定量逆转录PCR评估线粒体相关miRNA的表达差异。本研究数据表明，结直肠组织样本中MitomiRs；miR - 24、miR - 181、miR - 210、miR - 21和miR - 378的线粒体基因组表达在腺瘤性息肉之间存在差异。MitomiRs 24、181、210和378的表达从腺瘤性息肉的癌前阶段到腺癌逐渐增加。此外，与管状腺瘤相比，绒毛状腺瘤中miR - 210和miR - 181的表达增加了3倍，腺癌中miR378的表达增加超过3倍（<0.005）。同时，与绒毛状腺瘤组织相比，miR - 21在腺瘤组织中逐渐增加，但在腺癌中几乎降低了2.5倍（<0.001）。这些结果表明，MitomiRs可能调节重要的线粒体功能途径，为结直肠腺瘤性息肉转变或进展为腺癌创造更有利的环境。
