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miR-1290 通过靶向 INPP4B 促进结直肠癌细胞增殖。

miR-1290 Contributes to Colorectal Cancer Cell Proliferation by Targeting INPP4B.

机构信息

Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, P.R. China.

Department of Respiratory Medicine, Liaocheng People's Hospital, Liaocheng, P.R. China.

出版信息

Oncol Res. 2018 Sep 14;26(8):1167-1174. doi: 10.3727/096504017X15051741798389. Epub 2017 Sep 15.

Abstract

Colorectal cancer (CRC) is one of the most common oncological conditions worldwide, to date. MicroRNA-1290 (miR-1290) has been demonstrated to regulate its progression. We studied the role of miR-1290 in CRC progression. The gene was upregulated in CRC tissues and cells. Its overexpression promoted CRC cell proliferation analyzed by MTT assay, colony formation assay, and soft agar growth assay. In addition, miR-1290 knockdown inhibited CRC cell proliferation. We also found that miR-1290 overexpression reduced the p27 level and increased cyclin D1 at both the mRNA and protein levels, whereas miR-1290 knockdown increased p27 and reduced cyclin D1, confirming miR-1290 promoted CRC cell proliferation. Inositol polyphosphate 4-phosphatase B (INPP4B) was the target of miR-1290. Luciferase reporter assay revealed that miR-1290 directly bound to the 3'-UTR of INPP4B; the mutated seed sites in miR-1290 abrogated this effect. Double knockdown of INPP4B and miR-1290 promoted CRC cell proliferation, suggesting miR-1290 promoted CRC cell proliferation by targeting INPP4B.

摘要

结直肠癌(CRC)是迄今为止全球最常见的肿瘤疾病之一。microRNA-1290(miR-1290)已被证明可以调节其进展。我们研究了 miR-1290 在 CRC 进展中的作用。该基因在 CRC 组织和细胞中上调。通过 MTT 分析、集落形成分析和软琼脂生长分析表明,其过表达促进了 CRC 细胞增殖。此外,miR-1290 敲低抑制了 CRC 细胞增殖。我们还发现,miR-1290 过表达降低了 p27 水平,并在 mRNA 和蛋白水平上增加了 cyclin D1,而 miR-1290 敲低增加了 p27 并降低了 cyclin D1,证实了 miR-1290 促进了 CRC 细胞增殖。肌醇多磷酸 4-磷酸酶 B(INPP4B)是 miR-1290 的靶标。荧光素酶报告基因分析显示,miR-1290 直接结合 INPP4B 的 3'-UTR;miR-1290 中的突变种子位点消除了这种作用。INPP4B 和 miR-1290 的双重敲低促进了 CRC 细胞增殖,表明 miR-1290 通过靶向 INPP4B 促进 CRC 细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3ac/7844673/7d18db474484/OR-26-1167-g001.jpg

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