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pISSN 1226-4512 eISSN 2093-3827

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Original Article

Korean J Physiol Pharmacol 2024; 28(3): 265-273

Published online May 1, 2024 https://doi.org/10.4196/kjpp.2024.28.3.265

Copyright © Korean J Physiol Pharmacol.

RNA polymerase I subunit D activated by Yin Yang 1 transcription promote cell proliferation and angiogenesis of colorectal cancer cells

Jianfeng Shan, Yuanxiao Liang, Zhili Yang, Wenshan Chen, Yun Chen, and Ke Sun*

Department of Colorectal Surgery, Xinchang People’s Hospital, Xinchang, Zhejiang 312500, China

Correspondence to:Ke Sun
E-mail: 22673238@qq.com

Author contributions: J.S. and K.S. conceived the ideas. J.S., K.S., and Y.L. designed the experiments. J.S. and Y.L. performed the experiments. J.S., K.S., and Z.Y. analyzed the data. J.S., K.S., W.C., and Y.C. provided critical materials. J.S and W.C. wrote the manuscript. K.S. supervised the study. All the authors have read and approved the final version for publication.

Received: September 13, 2022; Revised: February 27, 2023; Accepted: April 25, 2023

Abstract

This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT- 29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Keywords: Colorectal neoplasms, POLR1D, p38 mitogen-activated protein kinases, YY1 transcription factor