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环状 FNDC3B 可将 miR-937-5p 隔离，解除 TIMP3 的抑制作用，并抑制结直肠癌细胞的进展。

CircFNDC3B sequestrates miR-937-5p to derepress TIMP3 and inhibit colorectal cancer progression.

机构信息

Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen, China.

Shenzhen University International Cancer Center, China.

出版信息

Mol Oncol. 2020 Nov;14(11):2960-2984. doi: 10.1002/1878-0261.12796. Epub 2020 Sep 19.

DOI:10.1002/1878-0261.12796
PMID:32896063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7607164/
Abstract

Circular RNA (circRNA) are single-stranded RNA with covalently closed 3' and 5' ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back-splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)-937-5p expression was high in CRC. MicroRNA-937-5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR-937-5p. CircFNDC3B and circFNDC3B-enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR-937-5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B-enriched exosomes or miR-937-5p knockdown. In conclusion, our work reports a tumor-suppressing role for the circFNDC3B-miR-97-5p-TIMP3 pathway and suggests that circFNDC3B-enriched exosomes can inhibit angiogenesis and CRC progression.

摘要

环状 RNA（circRNA）是具有共价闭合 3'和 5'末端的单链 RNA，许多被认为作为基因调节剂参与人类疾病，通常通过与其他 RNA 相互作用。CircFNDC3B 是由 FNDC3B 基因的外显子 5 和 6 反向剪接形成的 circRNA。CircFNDC3B 最近被牵连到肾癌、胃癌和膀胱癌中。然而，circFNDC3B 的表达水平及其在结直肠癌（CRC）中的作用仍不清楚。在 CRC 组织和细胞系中发现 circFNDC3B 和 TIMP3 水平表达较低，而 microRNA（miR）-937-5p 表达较高。miR-937-5p 下调 TIMP3，从而促进肿瘤细胞增殖、侵袭、迁移和血管生成。此外，CircFNDC3B 被证明与 miR-937-5p 结合。CircFNDC3B 和富含 CircFNDC3B 的外泌体抑制 CRC 的致瘤、转移和血管生成特性，而过表达 miR-937-5p 或敲低 TIMP3 可以逆转这些作用。在体内 CRC 肿瘤生长、血管生成和肝转移被 circFNDC3B 过表达、富含 CircFNDC3B 的外泌体或 miR-937-5p 敲低所抑制。总之，我们的工作报告了 circFNDC3B-miR-97-5p-TIMP3 通路的抑癌作用，并表明富含 CircFNDC3B 的外泌体可以抑制血管生成和 CRC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/9f2844e06978/MOL2-14-2960-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/4d987bffb0a1/MOL2-14-2960-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/a6cb5732517f/MOL2-14-2960-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/ea3e43b355d9/MOL2-14-2960-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/9f2844e06978/MOL2-14-2960-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/4d987bffb0a1/MOL2-14-2960-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/7f6021923060/MOL2-14-2960-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/718565d21636/MOL2-14-2960-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/d89536c66069/MOL2-14-2960-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/a731e22b3248/MOL2-14-2960-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/a6cb5732517f/MOL2-14-2960-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/ea3e43b355d9/MOL2-14-2960-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f535/7607164/9f2844e06978/MOL2-14-2960-g011.jpg

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