The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway

Author:

Zhu Yu-Heng1,Jia Qin-Yuan1,Yao Hong-Fei2,Duan Zong-Hao1,Ma Xue-Shi-Yu1,Zheng Jia-Hao3,Yin Yi-Fan1,Liu Wei1,Zhang Jun-Feng1,Hua Rong1,Ma Ding1,Sun Yong-Wei1,Yang Jian-Yu1,Liu De-Jun1,Huo Yan-Miao1

Affiliation:

1. Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

2. Fudan University

3. Shanghai Cancer Institute, Shanghai Jiao Tong University

Abstract

Abstract Background This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). Methods LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. Results LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. Conclusions Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Publisher

Research Square Platform LLC

Reference58 articles.

1. Cancer statistics, 2022;Siegel RL;Cancer J Clin,2022

2. Pancreatic cancer;Mizrahi JD;Lancet (London England),2020

3. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment;Wood LD;Gastroenterology,2022

4. Pancreatic cancer: Advances and challenges;Halbrook CJ;Cell,2023

5. New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer;Yao ZT;Cancer Commun (London England),2022

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3