长链非编码RNA AC245100.4通过上调蛋白酶激活受体2（PAR2）激活PI3K/AKT信号通路，促进前列腺癌细胞增殖。

Long non-coding RNA AC245100.4 activates the PI3K/AKT pathway to promote PCa cell proliferation by elevating PAR2.

作者信息

Zhang Ke, Liu Chi, Hu Changbin, Lin Ping, Qi Qi, Jia Huizhen, Tang Jiebing, Yu Xiaoguang

机构信息

Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150086, China.

Department of Rehabilitation, University-Town Hospital of Chongqing Medical University, Chongqing, 40016, China.

出版信息

Heliyon. 2023 Jun 3;9(6):e16870. doi: 10.1016/j.heliyon.2023.e16870. eCollection 2023 Jun.

DOI:10.1016/j.heliyon.2023.e16870

PMID:37346322

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10279817/

Abstract

BACKGROUND

Prostate cancer (PCa) is among the most generally diagnosed cancers in males. A long non-coding RNA (lncRNA) called AC245100.4 has been discovered and linked to PCa carcinogenesis. However, its specific and potential mechanism is uncertain in PCa. In this research, we investigated the role of AC245100.4 in cell proliferation and the underlying mechanism in PCa cells.

METHODS

qRT-PCR assays were utilized to detect AC245100.4 expression and confirm its downstream target. The pathways related to AC245100.4 were identified by RAP-MS. PCa cell proliferation was experimented by Cell Counting Kit-8 and Colony formation assays. Western blot was performed to detect PAR2, AKT, p-AKT, Cyclin D1 and PCNA expression.

RESULTS

AC245100.4/PAR2 overexpression promotes PCa cell proliferation and the opposite results are obtained after AC245100.4/PAR2 knockdown. Mechanistically, we found that PAR2 is confirmed as the AC245100.4 downstream target and AC245100.4 promotes PCa cell proliferation by regulating PAR2. AC245100.4 promotes PCa cell proliferation via PI3K/AKT pathway. Rescue assays validated that PAR2 knockdown reversed the impact of AC245100.4 overexpression on increasing p-AKT protein levels.

CONCLUSION

This research revealed that AC245100.4 enhances cell proliferation in PCa cells through modulating the PAR2/PI3K/AKT axis, which may offer novel tumor markers and potential therapeutic targets for PCa.

摘要

背景

前列腺癌（PCa）是男性中最常被诊断出的癌症之一。一种名为AC245100.4的长链非编码RNA（lncRNA）已被发现并与PCa的致癌作用相关。然而，其在PCa中的具体和潜在机制尚不清楚。在本研究中，我们研究了AC245100.4在PCa细胞增殖中的作用及其潜在机制。

方法

采用qRT-PCR检测AC245100.4的表达并确认其下游靶点。通过RAP-MS鉴定与AC245100.4相关的信号通路。采用细胞计数试剂盒-8和集落形成实验检测PCa细胞增殖情况。通过蛋白质免疫印迹法检测PAR2、AKT、p-AKT、细胞周期蛋白D1和增殖细胞核抗原（PCNA）的表达。

结果

AC245100.4/PAR2过表达促进PCa细胞增殖，而AC245100.4/PAR2敲低后则得到相反的结果。机制上，我们发现PAR2被确认为AC245100.4的下游靶点，AC245100.4通过调节PAR2促进PCa细胞增殖。AC245100.4通过PI3K/AKT信号通路促进PCa细胞增殖。挽救实验证实，PAR2敲低可逆转AC245100.4过表达对增加p-AKT蛋白水平的影响。