1. Academic Validation
  2. High expression of RUNX1 in colorectal cancer subtype accelerates malignancy by inhibiting HMGCR

High expression of RUNX1 in colorectal cancer subtype accelerates malignancy by inhibiting HMGCR

  • Pharmacol Res. 2024 Aug:206:107293. doi: 10.1016/j.phrs.2024.107293.
Zhilin Chang 1 Bing Liu 2 Han He 3 Xiaoyan Li 4 Hui Shi 5
Affiliations

Affiliations

  • 1 Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: zlchang372901@163.com.
  • 2 Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China.
  • 3 Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China. Electronic address: hehan_18@163.com.
  • 4 Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: lixiaoyan@bjtth.org.
  • 5 Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: shihui910728@163.com.
Abstract

Colorectal Cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing Apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and Cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated Cholesterol levels that subsequently hindered Cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on Cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.

Keywords

Cholesterol synthesis; Colorectal cancer; HMGCR; RUNX1; Therapeutic target.

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