ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer

Abstract

Aberrant expression of zinc-finger proteins has been extensively reported to contribute to malignant progression in a variety of cancers. However, clinical significance and biological roles of ZNF280A in the field of cancer are poorly known. In this study, the expression of ZNF280A was detected in clinical colorectal cancer (CRC) tissues. Functional experiments in vitro and animal experiment in vivo were performed to measure the effect of ZNF280A on the proliferation and tumorigenesis in CRC cells. Western blot and luciferase assays were used to identify the underlying pathway mediating the biological roles of ZNF280A in CRC. Here we report that ZNF280A was upregulated in CRC tissues and cells and a high expression of ZNF280A correlated with tumor, lymph node, and metastasis (TNM) classifications, clinical stage, and predicted poor prognosis and disease progression in CRC patients. Moreover, silencing ZNF280A repressed proliferation and induced G0 and/or G1 arrest in vitro , and it inhibited tumorigenesis of CRC cells in vivo . Our results further demonstrate that silencing ZNF280A inhibited the proliferation of CRC cells by activating Hippo signaling. Therefore, our results uncover a novel mechanistic understanding of ZNF280A-mediated tumor progression in CRC, and meanwhile they provide a novel prognostic factor in CRC patients and a potential therapeutic target for the treatment of CRC.

Circ0106714 inhibits tumorigenesis of colorectal cancer by sponging miR‐942‐5p and releasing DLG2 via Hippo‐YAP signaling

“…vating β-catenin. 36,37 In our previous study, 26,27 we explored the role of the Hippo signaling pathway in CRC. By performing bioinformatic analysis and cell experiments, we found that DLG2, the target gene of miR-942-5p, was also with a player in the Hippo signaling pathway.…”

“…In our previous studies, we found that aberrant Hippo signaling participated in CRC progression. 26,27 Hence, we pondered whether the positive regulation of DLG2 was related to CRC inhibition via the Hippo signaling pathway. Plenty of evidence suggests that hippo signaling activation is a hall marker of tumorigenesis.…”

“…In our previous study, we found that the Hippo signaling pathway played a regulatory role in CRC progression. 26,27 For this reason, we were highly interested in the upstream regulator of the Hippo signaling pathway in CRC. By analyzing the GSE126095 data series (using the GPL21047 platform) and selection criteria of adjusted p value of less than .01 and logFC < −1.5, we identified that 889 DEGs genes were in the hippo signaling pathway.…”

“…17 The Hippo signaling pathway, on the other hand, controls the size of organs; it is extensively associated with various tumors, including cancer of the liver, [18][19][20] breast, [21][22][23] lung, 24,25 and rectum. 26,27 DLG2 is an upstream effector of the Hippo signaling pathway, yet its function on CRC has never been studied before. YES-associated protein (YAP), on the other hand, is a vital downstream effector of the Hippo signaling pathway and is a direct downstream target of DLG2.…”

Knockdown of ZNF280A inhibits the development and progression of ovarian cancer

“…ZNF280A has been reported to be absent in hematopoietic malignancies, including peripheral cell lymphoma and chronic lymphocytic leukemia, suggesting that ZNF280A may play a role in tumor suppression in hematopoietic malignancies [27]. Conversely, Wang et al, suggested that ZNF280A promotes effort and tumorigenicity via inactivating the Hippo-signaling pathway in colorectal cancer [28]. The above findings on ZNFs in other cancers prompt us to explore the role of ZNF280A in OC.…”