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环指蛋白 2 通过抑制早期生长反应 1 促进结直肠癌的进展。

Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1.

机构信息

Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, China.

Department of Anorectal Surgery, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin 300013, China.

出版信息

Aging (Albany NY). 2020 Dec 19;12(24):26199-26220. doi: 10.18632/aging.202396.

DOI:10.18632/aging.202396
PMID:33346749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7803491/
Abstract

Ring finger protein 2 (RNF2) is an important component of polycomb repressive complex 1. RNF2 is upregulated in many kinds of tumors, and elevated RNF2 expression is associated with a poor prognosis in certain cancers. To assess the function of RNF2 in colorectal cancer, we examined RNF2 protein levels in 313 paired colorectal cancer tissues and adjacent normal tissues. We then analyzed the association of RNF2 expression with the patients' clinicopathologic features and prognoses. RNF2 expression was upregulated in colorectal cancer tissues and was associated with the tumor differentiation status, tumor stage and prognosis. In colorectal cancer cell lines, downregulation of RNF2 inhibited cell proliferation and induced apoptosis. Gene microarray analysis revealed that early growth response 1 (EGR1) was upregulated in RNF2-knockdown cells. Knocking down EGR1 partially reversed the inhibition of cell proliferation and the induction of apoptosis in RNF2-knockdown cells. RNF2 was enriched at the EGR1 promoter, where it mono-ubiquitinated histone H2A, thereby inhibiting EGR1 expression. These results indicate that RNF2 is oncogenic in colorectal cancer and may promote disease progression by inhibiting EGR1 expression. RNF2 is thus a potential prognostic marker and therapeutic target in colorectal cancer.

摘要

环指蛋白 2（RNF2）是多梳抑制复合物 1 的重要组成部分。RNF2 在许多类型的肿瘤中上调，并且升高的 RNF2 表达与某些癌症的不良预后相关。为了评估 RNF2 在结直肠癌中的功能，我们检查了 313 对结直肠癌组织和相邻正常组织中的 RNF2 蛋白水平。然后，我们分析了 RNF2 表达与患者临床病理特征和预后的关系。RNF2 在结直肠癌组织中上调，与肿瘤分化状态、肿瘤分期和预后相关。在结直肠癌细胞系中，下调 RNF2 抑制细胞增殖并诱导细胞凋亡。基因微阵列分析显示，早期生长反应 1（EGR1）在 RNF2 敲低细胞中上调。敲低 EGR1 部分逆转了 RNF2 敲低细胞中对细胞增殖的抑制和诱导凋亡。RNF2 在 EGR1 启动子处富集，在那里它单泛素化组蛋白 H2A，从而抑制 EGR1 的表达。这些结果表明，RNF2 在结直肠癌中是致癌的，可能通过抑制 EGR1 的表达促进疾病进展。因此，RNF2 是结直肠癌潜在的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/4d8760bea374/aging-12-202396-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/1c9fcf57ee2d/aging-12-202396-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/c722b451d6f6/aging-12-202396-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/fff17cbd317a/aging-12-202396-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/fbdfa78614cc/aging-12-202396-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/4d8760bea374/aging-12-202396-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/1c9fcf57ee2d/aging-12-202396-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/c722b451d6f6/aging-12-202396-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/fff17cbd317a/aging-12-202396-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/fbdfa78614cc/aging-12-202396-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7eb/7803491/4d8760bea374/aging-12-202396-g005.jpg

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