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长链非编码 RNA KTN1-AS1 通过 miR-885-5p/STRN3 轴促进食管鳞状细胞癌进展。

LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis.

机构信息

Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.

Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, Hebei, 050011, China.

出版信息

Genes Genomics. 2024 Feb;46(2):241-252. doi: 10.1007/s13258-023-01451-0. Epub 2023 Sep 25.

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and frequent cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) play regulatory roles and serve as biomarkers of multiple cancers, including ESCC. Our previous studies have confirmed that lncRNA Kinectin 1 antisense RNA 1 (KTN1-AS1) is highly expressed in ESCC and exerts oncogene function through RBBP4/HDAC1 complex.

OBJECTIVE

Our present study focused on exploring a novel molecular mechanism of KTN1-AS1 in ESCC.

METHODS

In this study, qRT-PCR assay, Western blot assay, Luciferase reporter assay, and RNA immunoprecipitation assay were conducted.

RESULTS

We found that KTN1-AS1 could bind to miR-885-5p in ESCC cells, and miR-885-5p was low expressed in ESCC. Overexpression of miR-885-5p inhibited esophageal cancer cells proliferation and invasion in vitro. Mechanistic analysis demonstrated that miR-885-5p specifically targeted striatin 3 (STRN3), and KTN1-AS1/miR-885-5p promoted the EMT process by Hippo pathway in STRN3/YAP1 dependent manner.

CONCLUSION

To sum up, KTN1-AS1 facilitates ESCC progression by acting as a ceRNA for miR-885-5p to regulate STRN3 expression and the Hippo pathway, and KTN1-AS1 maybe used as a promising therapeutic target for ESCC.

摘要

背景

食管鳞状细胞癌(ESCC)是最常见的恶性肿瘤之一,也是全球癌症相关死亡的常见原因。长链非编码 RNA(lncRNA)在多种癌症中发挥着调控作用,并作为生物标志物。我们之前的研究已经证实,lncRNA Kinectin 1 反义 RNA 1(KTN1-AS1)在 ESCC 中高表达,并通过 RBBP4/HDAC1 复合物发挥致癌基因功能。

目的

本研究旨在探讨 KTN1-AS1 在 ESCC 中的一种新的分子机制。

方法

本研究采用 qRT-PCR 检测、Western blot 检测、荧光素酶报告基因检测和 RNA 免疫沉淀检测。

结果

我们发现 KTN1-AS1 可以与 ESCC 细胞中的 miR-885-5p 结合,而 miR-885-5p 在 ESCC 中低表达。miR-885-5p 的过表达可抑制食管癌细胞的体外增殖和侵袭。机制分析表明,miR-885-5p 特异性靶向 striatin 3(STRN3),KTN1-AS1/miR-885-5p 通过 STRN3/YAP1 依赖性 Hippo 通路促进 EMT 过程。

结论

综上所述,KTN1-AS1 通过作为 miR-885-5p 的 ceRNA 来调节 STRN3 表达和 Hippo 通路,促进 ESCC 进展,KTN1-AS1 可能成为 ESCC 有前途的治疗靶点。

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