WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer

Zhi Yang,Wenxian Guan,Zijian Li,Xingzhou Wang,Min Feng,En Xu,Chao Wang,Jie Zhang,Hao Wang,Fengcen Lin,Heng Yu

doi:10.1186/s12935-021-02109-1

Zhi Yang, Wenxian Guan + Show 9 more

Open Access

https://doi.org/10.1186/s12935-021-02109-1

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Abstract

BackgroundWD40 repeat (WDR)43 is an RNA-binding protein that belongs to the WDR domain protein family. Its biological function is largely unclear, particularly in colorectal cancer (CRC).MethodsIn the present study, we searched the TCGA database and found the correlation between WDR43 and CRC. Subsequently, the high expression of WDR43 in human clinical samples of CRC was validated and we further examined the biological functions of it in CRC cells. Finally, we explored potential downstream proteins or pathways and established subcutaneous xenograft model to verify our findings.ResultsImmunohistochemistry of 16 patient specimens confirmed that the expression of WDR43 was elevated in CRC. WDR43 knockdown was shown to increase apoptosis and inhibit the proliferation, migration and invasion of CRC cells in vitro and reduce tumorigenesis in animal models. In addition, it was found that WDR43 knockdown inhibited vimentin (VIM) expression in CRC cells and overexpression of VIM can partially reverse the effects of WDR43 both in vitro and in vivo.ConclusionIn conclusion, the role of WDR43 in the occurrence and development of CRC was investigated in the present study. WDR43 may serve as a valuable biomarker and provide new options for the diagnosis and treatment of colorectal cancer.

Highlights

Colorectal cancer (CRC) accounts for 10% of the total cases of cancer and cancer-related mortality worldwide per annum [1]
WD40 repeat 43 (WDR43) is associated with the stage and tissue subtypes of CRCFollowing a search of the TCGA database, the expression of WDR43 was found to be increased in colorectal cancer (CRC), as compared to that in cancer-adjacent normal colon tissue (Fig. 1a)
WDR43 is highly expressed in CRC cells The level of WDR43 mRNA was detected in 4 CRC cell lines and the NCM460 human normal colonic epithelial cell line (Fig. 3a)

Summary

Introduction

Colorectal cancer (CRC) accounts for 10% of the total cases of cancer and cancer-related mortality worldwide per annum [1]. The WDR43 protein belongs to the protein family containing the WDR domain It is usually involved in the assembly of small-subunit processome as a conserved component, and mediates the transcription and processing of small-subunit ribosomal RNA (18S rRNA), which plays a key role in the biogenesis of ribosomes [8, 9]. WDR43 mutations were found to cause defects in craniofacial development in zebrafish [11], but were associated with the occurrence of human estrogen receptor-negative breast cancer [12]. These findings suggested that WDR43 plays a key role in cell proliferation and may be involved in the occurrence and development of cancer. Its biological function is largely unclear, in colorectal cancer (CRC)

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Discussion

Conclusion