Emami Sahar Sarmasti, Akbari Abolfazl, Zare Ali-Akbar, Agah Shahram, Masoodi Mohsen, Talebi Atefeh, Minaeian Sara, Fattahi Azam, Moghadamnia Farahnaz
Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Gastrointest Cancer. 2019 Jun;50(2):276-284. doi: 10.1007/s12029-018-0055-x.
Non-coding RNAs have opened a new window in cancer biology. MicroRNAs (miRNAs), as a family of non-coding RNAs, play an important role in the gene regulation. The aberrant expression of these small molecules has been documented to involve in colorectal cancer (CRC) pathogenesis. This study aimed to examine the expression of miRNAs in CRC and to correlate their expression levels with histological markers (Ki-67 and CD34).
Tumor tissues and matched normal adjacent tissues were collected from 36 patients with newly diagnosed CRC. Immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. A polyadenylation SYBER Green quantitative real-time PCR technique was used to quantify the expression of a panel of five CRC-related miRNAs (hsa-miR-21, 31, 20a, 133b, and 145). Histopathological (H) scores and miRNA expression levels were correlated with clinicopathological features including the degree of differentiation, staging, and lymphovascular invasion.
Our results showed the significant difference between the two groups for the expression level of hsa-miR-21, hsa-miR-31, hsa-miR-145, and miR-20a (P < 0.001), but not for hsa-miR-133b (P = 0.57). Further analysis revealed an inverse significant correlation between hsa-miR-145 and Ki-67 (r = - 0.942, P < 0.001). While a positive correlation was observed between hsa-miR-21 and Ki-67 (r = 0.920, P < 0.001), and hsa-miR-21 and CD34 (r = 0.981, P < 0.001). Also, a positive correlation between hsa-miR-31 and Ki-67 (r = 0.913, P < 0.001), hsa-miR-31 and CD34 (r = 0.798, P < 0.05), hsa-miR-20a and Ki-67 (r = 0.871, P < 0.001), and hsa-miR-20a and CD34 (r = 0.890, P < 0.001) was found.
Dysregulation of miRNAs and correlation with molecular histopathology indicate a biological role for miRNAs in various cellular processes including cell proliferation and angiogenesis in CRC development. On the other hand, the pattern of miRNA expression and its correlation with histological markers are potentially valuable to apply as diagnostic biomarkers for CRC.
非编码RNA在癌症生物学领域开启了一扇新窗口。微小RNA（miRNA）作为一类非编码RNA，在基因调控中发挥着重要作用。这些小分子的异常表达已被证明与结直肠癌（CRC）的发病机制有关。本研究旨在检测CRC中miRNA的表达，并将其表达水平与组织学标志物（Ki-67和CD34）相关联。
收集36例新诊断CRC患者的肿瘤组织及配对的正常相邻组织。对肿瘤组织进行免疫组织化学（IHC）染色以检测Ki-67（增殖）和CD34（血管生成）标志物，并获得免疫表达染色评分。采用聚腺苷酸化SYBER Green定量实时PCR技术定量检测一组5种与CRC相关的miRNA（hsa-miR-21、31、20a、133b和145）的表达。组织病理学（H）评分和miRNA表达水平与包括分化程度、分期和淋巴管浸润在内的临床病理特征相关。
我们的结果显示，两组之间hsa-miR-21、hsa-miR-31、hsa-miR-145和miR-20a的表达水平存在显著差异（P < 0.001），但hsa-miR-133b无显著差异（P = 0.57）。进一步分析显示，hsa-miR-145与Ki-67之间存在显著负相关（r = - 0.942，P < 0.001）。而hsa-miR-21与Ki-67之间呈正相关（r = 0.920，P < 0.001），hsa-miR-21与CD34之间也呈正相关（r = 0.981，P < 0.001）。此外，还发现hsa-miR-31与Ki-67之间呈正相关（r = 0.913，P < 0.001），hsa-miR-31与CD34之间呈正相关（r = 0.798，P < 0.05），hsa-miR-20a与Ki-67之间呈正相关（r = 0.871，P < 0.001），hsa-miR-20a与CD34之间呈正相关（r = 0.890，P < 0.001）。
miRNA的失调及其与分子组织病理学的相关性表明，miRNA在CRC发生发展的各种细胞过程（包括细胞增殖和血管生成）中具有生物学作用。另一方面，miRNA表达模式及其与组织学标志物的相关性作为CRC的诊断生物标志物具有潜在价值。
