Zinc finger protein 384 enhances colorectal cancer metastasis by upregulating MMP2

Yan,Zaihua; Zhou,Yu; Yang,Yang; Zeng,Chongpu; Li,Peidong; Tian,Hongpeng; Tang,Xuegui; Zhang,Guangjun

doi:10.3892/or.2022.8260

Zinc finger protein 384 enhances colorectal cancer metastasis by upregulating MMP2

Authors:
- Zaihua Yan
- Yu Zhou
- Yang Yang
- Chongpu Zeng
- Peidong Li
- Hongpeng Tian
- Xuegui Tang
- Guangjun Zhang
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Affiliations: Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Dermatology, Xining First People's Hospital, Xining, Qinghai 810000, P.R. China, Department of General Surgery, Wangcang County People's Hospital, Guangyuan, Sichuan 628200, P.R. China, Anorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
Published online on: January 12, 2022 https://doi.org/10.3892/or.2022.8260
Article Number: 49
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Zinc finger proteins (ZNFs) serve key roles in tumor formation and progression; however, the functions and underlying mechanisms of dysregulated ZNF384 in colorectal cancer (CRC) are yet to be fully elucidated. Therefore, the present study initially aimed to investigate the expression levels of ZNF384 in CRC samples. Moreover, lentiviral ZNF384 overexpression and ZNF384 knockdown models were established in CRC cells. Transwell, wound healing and in vivo tail vein metastasis assays were carried out to evaluate the effects of ZNF384 on CRC cell metastasis. Furthermore, reverse transcription‑quantitative PCR, western blotting, serial deletion, site‑directed mutagenesis, dual‑luciferase reporter and chromatin immunoprecipitation assays were conducted to investigate the potential underlying mechanisms. The results of the present study demonstrated that ZNF384 expression was markedly increased in CRC samples and this was associated with a poor prognosis. Notably, ZNF384 overexpression increased the levels of CRC cell invasion and migration, whereas ZNF384 knockdown inhibited CRC development. Moreover, the results of the present study demonstrated that ZNF384 mediated the expression of MMP2. MMP2 knockdown inhibited ZNF384‑mediated CRC cell invasion and migration, whereas MMP2 overexpression ameliorated ZNF384 knockdown‑induced inhibition of CRC progression. In addition, the results of the present study demonstrated that hypoxia‑inducible factor 1α (HIF‑1α) had the ability to bind to the ZNF384 promoter, thereby initiating ZNF384 expression. In human‑derived CRC samples, the expression levels of ZNF384 were positively correlated with both MMP2 and HIF‑1α expression. Collectively, these findings highlighted that ZNF384 may act as a prognostic marker and regulator of CRC metastasis.

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