Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.

Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with difficult treatment and poor prognosis, whose pathogenesis could be associated with the expression patterns of circular RNAs (circRNAs). Here, we aim to investigate the effects and mechanism of hsa_circ_0006834 on iCCA proliferation. At fir...

Full description

Saved in:
Bibliographic Details
Main Authors: Ji Wang, Xinyue Qi, Wangqian Zhao, Ziyan Hao, Kehan Wang, Yuting Li, Yue Wang, Yunshan Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0329847
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849391028365164544
author Ji Wang
Xinyue Qi
Wangqian Zhao
Ziyan Hao
Kehan Wang
Yuting Li
Yue Wang
Yunshan Zhang
author_facet Ji Wang
Xinyue Qi
Wangqian Zhao
Ziyan Hao
Kehan Wang
Yuting Li
Yue Wang
Yunshan Zhang
author_sort Ji Wang
collection DOAJ
description Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with difficult treatment and poor prognosis, whose pathogenesis could be associated with the expression patterns of circular RNAs (circRNAs). Here, we aim to investigate the effects and mechanism of hsa_circ_0006834 on iCCA proliferation. At first, hsa_circ_0006834 was proved to suppress iCCA cells proliferation and induce autophagy following the construction of hsa_circ_0006834 vector. And hsa_circ_0006834 is negatively linked with the proliferation, migration and invasion of iCCA cells through autophagy. Subsequently, RNA pull-down and dual-luciferase reporter assays were performed to validate the hsa_circ_0006834-has-miR-637-NGFR regulatory network. It was demonstrated by qPCR and Western blot that hsa_circ_0006834 stimulates the AMPK-mTOR pathway and triggers autophagy via NGFR after si-NGFR was synthesized and transfected into iCCA cells. Ultimately, after the successful knockdown of AMPK, the role of the AMPK-mTOR pathway in hsa_circ_0006834 regulating autophagy and proliferation was verified. Taken together, our findings revealed that hsa_circ_0006834 activates the AMPK-mTOR pathway and autophagy to suppress iCCA proliferation by has-miR-637-NGFR network, indicating the potential of hsa_circ_0006834 as a biomarker for iCCA diagnosis and therapy.
format Article
id doaj-art-6c2de95a4f1c4ab7b3397587685a032b
institution Kabale University
issn 1932-6203
language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-6c2de95a4f1c4ab7b3397587685a032b2025-08-20T03:41:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01208e032984710.1371/journal.pone.0329847Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.Ji WangXinyue QiWangqian ZhaoZiyan HaoKehan WangYuting LiYue WangYunshan ZhangIntrahepatic cholangiocarcinoma (iCCA) is a malignancy with difficult treatment and poor prognosis, whose pathogenesis could be associated with the expression patterns of circular RNAs (circRNAs). Here, we aim to investigate the effects and mechanism of hsa_circ_0006834 on iCCA proliferation. At first, hsa_circ_0006834 was proved to suppress iCCA cells proliferation and induce autophagy following the construction of hsa_circ_0006834 vector. And hsa_circ_0006834 is negatively linked with the proliferation, migration and invasion of iCCA cells through autophagy. Subsequently, RNA pull-down and dual-luciferase reporter assays were performed to validate the hsa_circ_0006834-has-miR-637-NGFR regulatory network. It was demonstrated by qPCR and Western blot that hsa_circ_0006834 stimulates the AMPK-mTOR pathway and triggers autophagy via NGFR after si-NGFR was synthesized and transfected into iCCA cells. Ultimately, after the successful knockdown of AMPK, the role of the AMPK-mTOR pathway in hsa_circ_0006834 regulating autophagy and proliferation was verified. Taken together, our findings revealed that hsa_circ_0006834 activates the AMPK-mTOR pathway and autophagy to suppress iCCA proliferation by has-miR-637-NGFR network, indicating the potential of hsa_circ_0006834 as a biomarker for iCCA diagnosis and therapy.https://doi.org/10.1371/journal.pone.0329847
spellingShingle Ji Wang
Xinyue Qi
Wangqian Zhao
Ziyan Hao
Kehan Wang
Yuting Li
Yue Wang
Yunshan Zhang
Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
PLoS ONE
title Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
title_full Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
title_fullStr Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
title_full_unstemmed Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
title_short Hsa_circ_0006834 represses intrahepatic cholangiocarcinoma proliferation through activating AMPK-mTOR pathway and autophagy via has-miR-637-NGFR network.
title_sort hsa circ 0006834 represses intrahepatic cholangiocarcinoma proliferation through activating ampk mtor pathway and autophagy via has mir 637 ngfr network
url https://doi.org/10.1371/journal.pone.0329847
work_keys_str_mv AT jiwang hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT xinyueqi hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT wangqianzhao hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT ziyanhao hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT kehanwang hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT yutingli hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT yuewang hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork
AT yunshanzhang hsacirc0006834repressesintrahepaticcholangiocarcinomaproliferationthroughactivatingampkmtorpathwayandautophagyviahasmir637ngfrnetwork