Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, Queensland, 4222, Australia; Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, Bangladesh.
Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, Queensland, 4222, Australia; School of Medical Science and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
Exp Mol Pathol. 2018 Feb;104(1):98-107. doi: 10.1016/j.yexmp.2018.01.006. Epub 2018 Jan 11.
miR-142-5p was noted aberrantly expressed and plays important roles in different pathophysiological conditions in human. The present study aims to examine the expression of miR-142-5p and its association with clinicopathological factors in a large cohort of patients with colorectal cancer. In addition, the cellular effects of miR-142-5p and its interacting targets in colon cancer cells were investigated.
Expression of miR-142-5p in colorectal cancer tissues (n=125) and colon cancer cell lines were analysed using real-time polymerase chain reaction. In vitro assays (cell proliferation, wound healing and colony formation) were used to study the miR-142-5p induced cellular effects. Western blots were used to examine the modulation of FAM134B, KRAS, EPAS1 and KLF6 proteins expression followed by miR-142-5p expression-manipulation.
Significant high expression of miR-142-5p was noted in cancer tissues and cells when compared to the controls (p<0.001). Overexpression of miR-142-5p in patients with colorectal cancer was common (72%; 90/125). miR-142-5p overexpression was associated with cancer in the proximal colorectum and with B-raf positive patients (p=0.05). Exogenous overexpression of miR-142-5p resulted in significantly increased cell proliferation, colony formation, and wound healing capacities, whereas inhibition of endogenous miR-142-5p led reduced cancer growth properties. The cellular effects of miR-142-5p were mediated by the modulation of tumour suppressor KLF6 expression, as the expression of miR-142-5p and KLF6 protein are inversely correlated in colon cancer cells.
High miR-142-5p expression was associated with the biological aggressiveness of cancer. Thus, suppression of miR-142-5p could be a therapeutic strategy for patients with colorectal cancers.
miR-142-5p 的表达异常，在人类的不同病理生理条件下发挥重要作用。本研究旨在检测 miR-142-5p 在大量结直肠癌患者中的表达及其与临床病理因素的关系。此外，还研究了 miR-142-5p 在结肠癌细胞中的细胞效应及其相互作用的靶标。
采用实时聚合酶链反应分析结直肠癌组织（n=125）和结肠癌细胞系中 miR-142-5p 的表达。采用体外试验（细胞增殖、划痕愈合和集落形成）研究 miR-142-5p 诱导的细胞效应。采用 Western blot 检测 FAM134B、KRAS、EPAS1 和 KLF6 蛋白表达的调节，然后进行 miR-142-5p 表达调控。
与对照组相比，癌症组织和细胞中 miR-142-5p 的表达明显升高（p<0.001）。结直肠癌患者 miR-142-5p 过表达较为常见（72%；90/125）。miR-142-5p 过表达与近端结直肠癌和 B-raf 阳性患者有关（p=0.05）。外源性过表达 miR-142-5p 导致细胞增殖、集落形成和伤口愈合能力显著增加，而内源性 miR-142-5p 抑制导致癌症生长特性降低。miR-142-5p 的细胞效应是通过调节肿瘤抑制因子 KLF6 表达介导的，因为在结肠癌细胞中 miR-142-5p 和 KLF6 蛋白的表达呈负相关。
高 miR-142-5p 表达与癌症的生物学侵袭性有关。因此，抑制 miR-142-5p 可能是结直肠癌患者的一种治疗策略。
