Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer

Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and...

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Autores principales:	Jiehua He, Ziqiang Chu, Wei Lai, Qiusheng Lan, Yujie Zeng, Daning Lu, Shaowen Jin, Heyang Xu, Pengwei Su, Dong Yin, Zhonghua Chu, Lu Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Colorectal cancer circHERC4 Metastasis miR-556-5p CTBP2 E-cadherin Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/605068e1ab614e7d9426a970f4a0d348
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spelling	oai:doaj.org-article:605068e1ab614e7d9426a970f4a0d3482021-11-21T12:02:31ZCircular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer10.1186/s13045-021-01210-21756-8722https://doaj.org/article/605068e1ab614e7d9426a970f4a0d3482021-11-01T00:00:00Zhttps://doi.org/10.1186/s13045-021-01210-2https://doaj.org/toc/1756-8722Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Methods Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. Results We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC. Conclusions CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.Jiehua HeZiqiang ChuWei LaiQiusheng LanYujie ZengDaning LuShaowen JinHeyang XuPengwei SuDong YinZhonghua ChuLu LiuBMCarticleColorectal cancercircHERC4MetastasismiR-556-5pCTBP2E-cadherinDiseases of the blood and blood-forming organsRC633-647.5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Colorectal cancer circHERC4 Metastasis miR-556-5p CTBP2 E-cadherin Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Colorectal cancer circHERC4 Metastasis miR-556-5p CTBP2 E-cadherin Diseases of the blood and blood-forming organs RC633-647.5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jiehua He Ziqiang Chu Wei Lai Qiusheng Lan Yujie Zeng Daning Lu Shaowen Jin Heyang Xu Pengwei Su Dong Yin Zhonghua Chu Lu Liu Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
description	Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Methods Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. Results We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC. Conclusions CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.
format	article
author	Jiehua He Ziqiang Chu Wei Lai Qiusheng Lan Yujie Zeng Daning Lu Shaowen Jin Heyang Xu Pengwei Su Dong Yin Zhonghua Chu Lu Liu
author_facet	Jiehua He Ziqiang Chu Wei Lai Qiusheng Lan Yujie Zeng Daning Lu Shaowen Jin Heyang Xu Pengwei Su Dong Yin Zhonghua Chu Lu Liu
author_sort	Jiehua He
title	Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
title_short	Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
title_full	Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
title_fullStr	Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
title_full_unstemmed	Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
title_sort	circular rna circherc4 as a novel oncogenic driver to promote tumor metastasis via the mir-556-5p/ctbp2/e-cadherin axis in colorectal cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/605068e1ab614e7d9426a970f4a0d348
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Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer

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