ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer.
ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer.
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ERp29与microRNA-135a-5p形成反馈调节环，促进结直肠癌进展
DOI：
10.1038/s41419-021-04252-z
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发表时间：
2021-10-19
影响因子：
9
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Huang J;Jing M;Chen X;Gao Y;Hua H;Pan C;Wu J;Wang X;Chen X;Gao Y;Xu C;Li P
内质网（ER）应激相关基因的表达往往在癌症进展中失调。ER蛋白29（ERp 29）在多种肿瘤中异常表达，在肿瘤发生中起重要作用。在此，我们发现ERp 29是microRNA-135 a-5 p（miR-135 a-5 p）抑制结直肠癌（CRC）进展的新靶点;相应地，ERp 29作为癌蛋白在CRC中通过促进CRC细胞的增殖和转移以及抑制细胞的凋亡而起作用。更重要的是，我们发现ERp 29通过抑制IL-1β诱导的miR-135 a-5 p启动子区域甲基化来反向上调miR-135 a-5 p表达，这是肠细胞维持miR-135 a-5 p和ERp 29之间平衡的过程，但在CRC中失调。我们的研究揭示了miR-135 a-5 p和ERp 29之间的一种新的反馈调节环，这对维持它们各自的适当水平至关重要，但在CRC中部分失衡，导致miR-135 a-5 p和ERp 29的异常表达，这进一步加速了CRC的进展。我们为ERp 29和miR-135 a-5 p作为CRC诊断和治疗的潜在生物标志物提供了支持证据。
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.
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影响因子：
3.5
作者：
Demmer, J;Zhou, CM;Hubbard, MJ
通讯作者：
Hubbard, MJ
影响因子：
32.4
作者：
Dmitrieva-Posocco, Oxana;Dzutsev, Amiran;Grivennikov, Sergei, I
通讯作者：
Grivennikov, Sergei, I
影响因子：
14.9
作者：
Hubbard, T;Barker, D;Clamp, M
通讯作者：
Clamp, M
影响因子：
5.8
作者：
Feng, Lei;Lin, Tao;Wang, Xiaoming
通讯作者：
Wang, Xiaoming
ERp29对抗内质网应激介导的恶性肿瘤抑制并促进结直肠癌转移
影响因子：
4.2
作者：
Guo, Lili;Ma, Lili;Deng, Yongjian
通讯作者：
Deng, Yongjian