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LINC00958 通过靶向 miR-3619-5p 抑制结直肠癌细胞的增殖、侵袭和迁移,促进其凋亡。

Downregulation of LINC00958 inhibits proliferation, invasion and migration, and promotes apoptosis of colorectal cancer cells by targeting miR‑3619‑5p.

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Rep. 2020 Oct;44(4):1574-1582. doi: 10.3892/or.2020.7707. Epub 2020 Jul 29.

Abstract

The aberrant expression of long non‑coding RNAs (lncRNAs), including LINC00958, has been demonstrated in several types cancers. The present study aimed to investigate the role of LINC00958 in colorectal cancer (CRC) and identify the possible underlying mechanisms. The expression of LINC00958 and microRNA (miR)‑3619‑5p was detected in several human CRC cell lines using reverse transcription‑quantitative PCR. Then, short hairpin RNA (shRNA)‑LINC00958 was transfected into the cells. The results revealed that the expression of LINC00958 was notably upregulated, whereas miR‑3619‑5p was downregulated in CRC cells. Transfection with shRNA‑LINC00958 inhibited the proliferation, invasion and migration of CRC cells. Moreover, the rate of apoptosis was enhanced, accompanied by a decrease in the expression of Bcl‑2 and an increase in the expression of Bax and caspase‑3. A luciferase reporter assay was conducted to verify the target binding site between LINC00958 and miR‑3619‑5p. The luciferase reporter assay confirmed that miR‑3619‑5p could be directly targeted by LINC00958. Furthermore, the miR‑3619‑5p inhibitor reversed the effects of LINC00958 silencing on proliferation, invasion, migration and apoptosis. Taken together, the findings suggest that the downregulation of LINC00958 suppresses the proliferation, invasion and migration, and promotes the apoptosis of CRC cells by targeting miR‑3619‑5p in vitro, which provides a theoretical basis and therapeutic strategy for the treatment of CRC.

摘要

长链非编码 RNA(lncRNA)的异常表达,包括 LINC00958,已在几种类型的癌症中得到证实。本研究旨在探讨 LINC00958 在结直肠癌(CRC)中的作用,并确定其潜在的机制。采用逆转录定量 PCR 检测几种人 CRC 细胞系中 LINC00958 和 microRNA(miR)-3619-5p 的表达。然后,将短发夹 RNA(shRNA)-LINC00958 转染到细胞中。结果表明,CRC 细胞中 LINC00958 的表达明显上调,而 miR-3619-5p 的表达下调。转染 shRNA-LINC00958 抑制 CRC 细胞的增殖、侵袭和迁移。此外,细胞凋亡率增加,Bcl-2 表达减少,Bax 和 caspase-3 表达增加。进行荧光素酶报告基因实验验证 LINC00958 和 miR-3619-5p 之间的靶结合位点。荧光素酶报告基因实验证实 miR-3619-5p 可被 LINC00958 直接靶向。此外,miR-3619-5p 抑制剂逆转了 LINC00958 沉默对增殖、侵袭、迁移和凋亡的影响。综上所述,这些发现表明,下调 LINC00958 通过靶向 miR-3619-5p 在体外抑制 CRC 细胞的增殖、侵袭和迁移,并促进其凋亡,为 CRC 的治疗提供了理论依据和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e4/7448424/0e85fa58929b/OR-44-04-1574-g00.jpg

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