ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer.

Abstract

Expression of endoplasmic reticulum (ER) stress-associated genes is often dysregulated in cancer progression. ER protein 29 (ERp29) is abnormally expressed in many neoplasms and plays an important role in tumorigenesis. Here, we showed ERp29 is a novel target for microRNA-135a-5p (miR-135a-5p) to inhibit the progression of colorectal cancer (CRC); correspondingly, ERp29 acts as an oncoprotein in CRC by promoting proliferation and metastasis of CRC cells, and suppressing apoptosis of the cells. More importantly, we found that miR-135a-5p expression is reversely upregulated by ERp29 through suppressing IL-1β-elicited methylation of miR-135a-5p promoter region, a process for enterocyte to maintain a balance between miR-135a-5p and ERp29 but dysregulated in CRC. Our study reveals a novel feedback regulation loop between miR-135a-5p and ERp29 that is critical for maintaining appropriate level of each of them, but partially imbalanced in CRC, resulting in abnormal expression of miR-135a-5p and ERp29, which further accelerates CRC progression. We provide supporting evidence for ERp29 and miR-135a-5p as potential biomarkers for diagnosis and treatment of CRC.

• Authors: Jiebin Huang, Mengxia Jing, Xixi Chen, Yuanqi Gao, Huiying Hua, Chun Pan, Jing Wu, Xinqiong Wang, Xuehua Chen, Yujing Gao, Chundi Xu, Pu Li
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 11 Pg. 965 (10 19 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 34667160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• 3' Untranslated Regions
• ERP29 protein, human
• Heat-Shock Proteins
• Interleukin-1beta
• MIRN135 microRNA, human
• MicroRNAs

Topics

• 3' Untranslated Regions (genetics)
• Animals
• Apoptosis (drug effects, genetics)
• Base Sequence
• Binding Sites
• Carcinogenesis (drug effects, genetics, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects, genetics)
• Colorectal Neoplasms (genetics, pathology)
• DNA Methylation (drug effects, genetics)
• Disease Progression
• Down-Regulation (drug effects, genetics)
• Feedback, Physiological
• Gene Expression Regulation, Neoplastic (drug effects)
• Heat-Shock Proteins (genetics, metabolism)
• Humans
• Interleukin-1beta (pharmacology)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Neoplasm Metastasis