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环状STK3通过调节上皮-间质转化驱动结直肠癌转移。

CircSTK3 drives the metastasis of colorectal cancer by regulating epithelial-mesenchymal transition.

作者信息

Fan Boyang, Zheng Chaojing, Wang Ning, Chang Zewen, Liu Yunxiao, Wang Chunlin, Xiang Jun, Tao Yangbao, Wang Guiyu, Zhang Qian

机构信息

Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.

出版信息

iScience. 2023 Feb 9;26(3):106170. doi: 10.1016/j.isci.2023.106170. eCollection 2023 Mar 17.

DOI:10.1016/j.isci.2023.106170
PMID:36922993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10009203/
Abstract

Circular RNAs (circRNAs) play crucial roles in malignancies. We aimed to delineate the functions and clinical importance of dysregulated circRNAs in colorectal cancer (CRC). We determined the circRNA expression profile from five CRC and paired adjacent normal tissues using circRNA microarray. We found that a novel circRNA, hsa_circ_0004592 (named circSTK3), was significantly upregulated in CRC tissues and correlated with decreased survival. Loss- and gain-of-function assays revealed that circSTK3 promoted the migration and invasion but not proliferation of cells. Whole genome expression microarray identified potential downstream targets and the regulatory networks of circSTK3; Gene Ontology analysis confirmed circSTK3 involvement in the CRC metastasis phenotype. Abnormal circSTK3 expression affected a subset of genes associated with CRC metastasis and triggered epithelial-mesenchymal transition programming, maintaining a tumor-promoting signature. Moreover, circSTK3 was transcriptionally regulated by CTCF. These findings reveal the functional and prognostic roles of circSTK3 and expose circRNAs as key players in metastasis.

摘要

环状RNA（circRNAs）在恶性肿瘤中发挥着关键作用。我们旨在阐明失调的circRNAs在结直肠癌（CRC）中的功能及临床重要性。我们使用circRNA微阵列测定了5例CRC组织及其配对的相邻正常组织中的circRNA表达谱。我们发现一种新型circRNA，hsa_circ_0004592（命名为circSTK3），在CRC组织中显著上调，且与生存率降低相关。功能缺失和功能获得实验表明，circSTK3促进细胞迁移和侵袭，但不促进细胞增殖。全基因组表达微阵列确定了circSTK3的潜在下游靶点及其调控网络；基因本体分析证实circSTK3参与CRC转移表型。circSTK3的异常表达影响了与CRC转移相关的一部分基因，并触发上皮-间质转化程序，维持肿瘤促进特征。此外，circSTK3受CTCF转录调控。这些发现揭示了circSTK3的功能和预后作用，并表明circRNAs是转移中的关键参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/bb26530e872e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/59891275d834/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/f34ee391343b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/1fc673a4dd5e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/786508cc6ff0/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/38525da22067/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/7c5f71733e02/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/a3e28223b7ce/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/bb26530e872e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/59891275d834/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/f34ee391343b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/1fc673a4dd5e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/786508cc6ff0/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/38525da22067/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/7c5f71733e02/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/a3e28223b7ce/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f28/10009203/bb26530e872e/gr8.jpg

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