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长链非编码 RNA PCED1B-AS1 通过调控 miR-633/HOXA9 轴促进结直肠腺癌的增殖。

Long non-coding RNA PCED1B-AS1 promotes the proliferation of colorectal adenocarcinoma through regulating the miR-633/HOXA9 axis.

机构信息

Department of Gastrointestinal Surgery, Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, PR, China.

出版信息

Bioengineered. 2022 Mar;13(3):5407-5420. doi: 10.1080/21655979.2022.2037225.

DOI:10.1080/21655979.2022.2037225
PMID:35176937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8974004/
Abstract

Long non-coding RNA (lncRNA) PCED1B-AS1 was shown to play essential roles in human cancers, while its function in colorectal adenocarcinoma remains unclear. This study was carried out to investigate the function of PCED1B-AS1 in regulating the microRNA(miR)-633/HOXA9 axis in colorectal adenocarcinoma. The expression of PCED1B-AS1, miR-633 and HOXA9 was measured by quantitative real-time PCR (qRT-PCR) or Western blot analysis. Cell behaviors of colorectal adenocarcinoma cell lines were assessed by CCK-8, EdU, Transwell and flow cytometry assays. The interaction among PCED1B-AS1, miR-633 and HOXA9 was determined by luciferase reporter and RIP assays. Rescue experiments were performed to determine the regulatory axis in colorectal adenocarcinoma. Moreover, an animal model was established to verify the role of PCED1B-AS1. We found that PCED1B-AS1 was upregulated and miR-633 was downregulated in colorectal adenocarcinoma tissues and corresponding cell lines. Knockdown of PCED1B-AS1 inhibited cell proliferation and promoted apoptosis, while miR-633 inhibitor elevated proliferation and reduced apoptosis of cancer cell lines. In addition, overexpression of HOXA9 obviously attenuated the protective role of knockdown of PCED1B-AS1 or miR-633 mimics in colorectal adenocarcinoma progression. PCED1B-AS1 could negatively regulate the expression of HOXA9 by sponging miR-633. The experiments confirmed the role of PCED1B-AS1 and miR-633 in colorectal adenocarcinoma, as well as the regulatory relationship of this axis. Our results demonstrated that knockdown of PCED1B-AS1 inhibited the progression of colorectal adenocarcinoma by regulating the miR-633/HOXA9 axis.

摘要

长链非编码 RNA(lncRNA)PCED1B-AS1 被证明在人类癌症中发挥着重要作用,但其在结直肠腺癌中的作用尚不清楚。本研究旨在探讨 PCED1B-AS1 在调节结直肠腺癌细胞中 microRNA(miR)-633/HOXA9 轴中的作用。通过定量实时 PCR(qRT-PCR)或 Western blot 分析测量 PCED1B-AS1、miR-633 和 HOXA9 的表达。通过 CCK-8、EdU、Transwell 和流式细胞术测定结直肠腺癌细胞系的细胞行为。通过荧光素酶报告和 RIP 测定确定 PCED1B-AS1、miR-633 和 HOXA9 之间的相互作用。进行挽救实验以确定结直肠腺癌中的调节轴。此外,建立了动物模型以验证 PCED1B-AS1 的作用。我们发现 PCED1B-AS1 在结直肠腺癌组织和相应的细胞系中上调,而 miR-633 下调。PCED1B-AS1 的敲低抑制了细胞增殖并促进了细胞凋亡,而 miR-633 抑制剂则升高了癌细胞系的增殖并降低了凋亡。此外,HOXA9 的过表达明显减弱了敲低 PCED1B-AS1 或 miR-633 模拟物对结直肠腺癌进展的保护作用。PCED1B-AS1 可以通过海绵 miR-633 负调控 HOXA9 的表达。这些实验证实了 PCED1B-AS1 和 miR-633 在结直肠腺癌中的作用,以及该轴的调节关系。我们的结果表明,敲低 PCED1B-AS1 通过调节 miR-633/HOXA9 轴抑制结直肠腺癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/630d3579a73f/KBIE_A_2037225_F0008_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/d127970d92d0/KBIE_A_2037225_F0005_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/50cf5d183a58/KBIE_A_2037225_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/630d3579a73f/KBIE_A_2037225_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/503bdb788882/KBIE_A_2037225_UF0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/f10193bf73c2/KBIE_A_2037225_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/600039816a60/KBIE_A_2037225_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/d127970d92d0/KBIE_A_2037225_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/aadd486f60c9/KBIE_A_2037225_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/50cf5d183a58/KBIE_A_2037225_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/8974004/630d3579a73f/KBIE_A_2037225_F0008_OC.jpg

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