ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer |
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| 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 |
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| Institution: | 1.Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Er Rd.197, Shanghai, 200025 China ;2.Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032 China ;3.NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004 China |
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| 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.Subject terms: Cell death, Oncogenes |
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