Liu Xiaojian, Xing Chungen
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Transl Cancer Res. 2019 Aug;8(4):1289-1300. doi: 10.21037/tcr.2019.07.12.
BACKGROUND: Suppression of expression in colon cancer tissues may be associated with elevated levels of the microRNA 221 (miR-211). To uncover potential targets for treatment, the present study investigated in colon cancer development, and explored the role of miR-221-3p in the regulation of . METHODS: RNA expression arrays were searched in the NCBI database, and (PDZ domain containing ring finger 4) was selected as a potential downregulated gene in colon cancer. mRNA and protein in colon cancer and matched normal tissues were analyzed. The proliferation and dissemination of HCT116 cells overexpressing was assessed via functional assays. Bioinformatics analysis and luciferase reporter assay were applied to determine the regulatory link between miR-221-3p and mRNA. RESULTS: There was significantly less mRNA and protein in colon cancer tissue compared with normal tissues. HCT116 cells overexpressing were less able to disseminate relative to the control. Expression of was directly inhibited by miR-221-3p. Knockout of miR-211-3p was associated with attenuated proliferation and dissemination of HCT116 cells. CONCLUSIONS: may function as a tumor suppressor and is downregulated in colon cancer tissues, possibly due to dysregulation via miR-221-3p. This study provides new insight into colon cancer development.
背景:结肠癌组织中[某基因]表达的抑制可能与微小RNA 221(miR - 221)水平升高有关。为了揭示潜在的治疗靶点,本研究调查了[某基因]在结肠癌发生发展中的作用,并探讨了miR - 221 - 3p在[某基因]调控中的作用。 方法:在NCBI数据库中检索RNA表达阵列,并选择[含PDZ结构域的环指蛋白4(PDZ domain containing ring finger 4)]作为结肠癌中潜在的下调基因。分析结肠癌组织和配对的正常组织中[该基因]的mRNA和蛋白。通过功能实验评估过表达[该基因]的HCT116细胞的增殖和扩散情况。应用生物信息学分析和荧光素酶报告基因实验来确定miR - 221 - 3p与[该基因]mRNA之间的调控联系。 结果:与正常组织相比,结肠癌组织中[该基因]的mRNA和蛋白显著减少。相对于对照组,过表达[该基因]的HCT116细胞扩散能力较弱。[该基因]的表达受到miR - 221 - 3p的直接抑制。敲除miR - 211 - 3p与HCT116细胞增殖和扩散减弱有关。 结论:[该基因]可能作为一种肿瘤抑制因子,在结肠癌组织中表达下调,可能是由于miR - 221 - 3p调控异常所致。本研究为结肠癌的发生发展提供了新的见解。
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