长链非编码 RNA 01857 通过调控 microRNA-197-3p/前梯度 2 轴在肝癌恶性进展中的作用。
Role of long intergenic non-protein coding RNA 01857 in hepatocellular carcinoma malignancy via the regulation of the microRNA-197-3p/anterior GRadient 2 axis.
机构信息
Department of Hepatopancreatobiliary Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
出版信息
PLoS One. 2021 Nov 18;16(11):e0258312. doi: 10.1371/journal.pone.0258312. eCollection 2021.
OBJECTIVE
This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis.
METHODS
LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC.
RESULTS
LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC.
CONCLUSION
The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.
目的
本研究旨在探讨长链非编码 RNA（LINC）01857 在肝细胞癌（HCC）增殖和凋亡中的差异表达及其机制。
方法
评估 LINC01857 在 HCC 组织和细胞中的表达。此外，通过获得和缺失功能来评估 HCC 细胞的增殖和凋亡。之后，预测并验证 LINC01857 的亚细胞定位。此外，检测并证实 LINC01857 与 microRNA（miRNA）-197-3p 之间以及 miR-197-3p 与 anterior GRadient 2（AGR2）之间的结合关系。另外，沉默 LINC01857 或过表达 AGR2 后评估 HCC 细胞的增殖和凋亡。接下来，测量 AKT 和 ERK 通路中的关键因子水平。此外，还进行了异种移植移植以确认 LINC01857 在 HCC 中的作用。
结果
LINC01857 在 HCC 中高表达。沉默 LINC01857 导致 HCC 细胞增殖受阻但凋亡改善。LINC01857 可以竞争性地与 miR-197-3p 结合，从而上调 AGR2。miR-197-3p 在 HCC 中表达水平较低，而 AGR2 表达水平较高。机制上，下调 miR-197-3p 或过表达 AGR2 观察到可减弱 LINC01857 敲低对抑制细胞增殖和增强凋亡的作用。此外，LINC01857 通过操纵 miR-197-3p/AGR2 轴在 HCC 中激活 AKT 和 ERK 通路。
结论
本研究结果表明，LINC01857 在 HCC 中高表达，可通过竞争性结合 miR-197-3p，促进 AGR2 并上调 AKT 和 ERK 通路，从而提高 HCC 细胞增殖并减少凋亡。
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