长链非编码 RNA PCED1B 反义 RNA 1 通过调控 microRNA-34a/CD44 轴促进肝癌细胞增殖和侵袭。
Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.
机构信息
Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Jinan, China.
The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518020, China.
出版信息
Curr Med Sci. 2024 Jun;44(3):503-511. doi: 10.1007/s11596-023-2823-5. Epub 2024 May 15.
OBJECTIVE
This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC).
METHODS
A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.
RESULTS
PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.
CONCLUSION
PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.
目的
本研究旨在探讨长链非编码 RNA PCED1B 反义 RNA 1（PCED1B-AS1）在肝细胞癌（HCC）发展中的作用。
方法
从 62 例 HCC 患者中获得 62 对 HCC 组织和相邻非肿瘤组织。通过双荧光素酶活性测定和 RNA 下拉测定检测 PCED1B-AS1 与 microRNA-34a（miR-34a）的相互作用。通过 RT-qPCR 检测 PCED1B-AS1、miR-34a 和 CD44 的 RNA 表达水平，通过 Western blot 测定 CD44 的蛋白表达水平。通过细胞增殖测定检测细胞增殖，通过 Transwell 侵袭测定检测细胞侵袭和迁移。通过体内动物研究确定下调 PCED1B-AS1 后 HCC 肿瘤的生长情况。
结果
PCED1B-AS1 在 HCC 组织中高表达，与 HCC 患者的生存不良相关。此外，PCED1B-AS1 在 HCC 细胞中与 miR-34a 相互作用，但它们彼此不调节表达。此外，PCED1B-AS1 增加了被 miR-34a 靶向的 CD44 的表达水平。细胞增殖和侵袭实验表明，miR-34a 抑制了 HCC 在体外的增殖和侵袭，而 CD44 则表现出相反的作用。此外，PCED1B-AS1 抑制了 miR-34a 的作用。此外，PCED1B-AS1 的敲低抑制了体内裸鼠 HCC 肿瘤的生长。
结论
PCED1B-AS1 可能通过调节 miR-34a/CD44 轴在 HCC 中发挥致癌作用。
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