Zinc finger of the cerebellum 5 promotes colorectal cancer cell proliferation and cell cycle progression through enhanced CDK1/CDC25c signaling

Abstract

Introduction: Colorectal cancer (CRC), mostly caused by external or environmental factors, is the third most common and lethal cancer worldwide. Although a large number of investigations have been carried out to reveal the evolution of CRC, the underlying mechanisms of CRC remain unclear. Material and methods: Expression of zinc finger of the cerebellum 5 (ZIC5) in CRC tissues and cell models was measured by qRT-PCR and IHC. Cell transfection was carried out for ZIC5 overexpression or knockdown. The MTT assay was applied to examine the capacity of glioma cell proliferation. Wound healing assay and tumor invasion assay were used to test the capacity of glioma cell migration and invasion respectively. Cell cycle analysis and western blot were used to verify the apoptosis rates of CRC cells upon ZIC5 overexpression or downregulation. A further tumor Xenograft study was used to examine the effects of ZIC5 on tumor malignancy in vivo. Results: Cell models using HCT116 and SW620 cells were established to study the ZIC5 function upon ZIC5 overexpression of knockdown. Consistently, we discovered that ZIC5 also significantly increased in Chinese CRC patients. In addition, ZIC5 promoted CRC cell proliferation through increasing the proportion of cells maintained in the S phase. ZIC5 overexpression facilitated the capacity of CRC cell migration and invasion. Inhibition of ZIC5 mitigated such malignant effects. Conclusions: Collectively, investigations of the ZIC5 in CRC provided a new insight into CRC diagnosis, treatment, prognosis and next-step translational therapeutic developments from bench to clinic.

ZIC5 promotes human hepatocellular carcinoma cell proliferation through upregulating COL1A1

“…Notably, knockdown of ZIC5 inhibited non-small cell lung cancer cell proliferation and led to cell cycle arrest in G2 phase (16). Another study confirmed that ZIC5 expression was significantly increased in Chinese patients with colorectal cancer, and ZIC5 increased the proportion of cells in S phase to accelerate colorectal cancer cell proliferation (25). Knockdown of ZIC5 in colorectal cancer cells increased glycolytic status and tolerance to low-glucose conditions (26).…”

Alterations in Gene Pair Correlations as Potential Diagnostic Markers for Colon Cancer

“…Zinc finger of the cerebellum 5 (ZIC5) is a transcriptional repressor. It plays an important role in colorectal cancer via regulating cell cycle progression and the modulation of CDC25/CDK/cyclin signaling [ 48 ]. Cystatin SN (cystatin 1, CST1) inhibits cysteine proteases and promotes cell proliferation and metastasis.…”

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

“…These in vitro results were validated in a mouse model with a smaller tumor size and weight, documented after silencing circ-HIPK3 [ 140 ]. ZIC5 is assiduously involved in promoting carcinogenesis [ 148 , 149 , 150 , 151 ]. Hence, the discovery and characterization of the axis, as mentioned earlier, could be a new way to treat recurrent high-grade glioblastoma.…”