TY - JOUR
T1 - NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-β/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer
AU - Liu, Shanshan
AU - He, Xiaomeng
AU - Di, Yang
AU - Li, Qiuyue
AU - Li, Feng
AU - Ma, Yan
AU - Chen, Litian
AU - Gao, Yushi
AU - Xu, Jingjing
AU - Yang, Shuai
AU - Xu, Li
AU - Corpe, Christopher
AU - Ling, Yun
AU - Zhang, Xiaoyan
AU - Xu, Jianqing
AU - Yu, Wenqiang
AU - Wang, Jin
N1 - © The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Funding Information:
This research was supported by a grant from the National Natural Science Foundation of China (81672383), a grant from Shanghai sailing program (19YF1441100), a grant from the Science and Technology Commission of Shanghai (20Y11900700), a grant (KY-GW-2020-09) from Shanghai Public Health Clinical Center and a grant from the Special Research Fund of Youan Medical Alliance for the Liver and Infectious Diseases (LM202020).
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press. All rights reserved.
PY - 2023/5/26
Y1 - 2023/5/26
N2 - Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-β/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-β, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-β/Smad3 pathway.
AB - Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-β/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-β, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-β/Smad3 pathway.
UR - http://www.scopus.com/inward/record.url?scp=85153413724&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgac102
DO - 10.1093/carcin/bgac102
M3 - Article
C2 - 36591938
SN - 0143-3334
VL - 44
SP - 153
EP - 165
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -
