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WD40重复序列43通过波形蛋白介导结直肠癌中的细胞存活、增殖、迁移和侵袭。

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

作者信息

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

机构信息

Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, People's Republic of China.

Department of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu, People's Republic of China.

出版信息

Cancer Cell Int. 2021 Aug 9;21(1):418. doi: 10.1186/s12935-021-02109-1.

DOI:10.1186/s12935-021-02109-1
PMID:34372874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8351096/
Abstract

BACKGROUND

WD40 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).

METHODS

In 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.

RESULTS

Immunohistochemistry 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.

CONCLUSION

In 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.

摘要

背景

WD40重复序列(WDR)43是一种RNA结合蛋白,属于WDR结构域蛋白家族。其生物学功能在很大程度上尚不清楚,尤其是在结直肠癌(CRC)中。

方法

在本研究中,我们检索了TCGA数据库,发现了WDR43与CRC之间的相关性。随后,我们验证了WDR43在人类CRC临床样本中的高表达,并进一步研究了其在CRC细胞中的生物学功能。最后,我们探索了潜在的下游蛋白或通路,并建立了皮下异种移植模型来验证我们的发现。

结果

对16例患者标本进行免疫组织化学检测,证实CRC中WDR43的表达升高。在体外,WDR43基因敲低可增加细胞凋亡,抑制CRC细胞的增殖、迁移和侵袭,并在动物模型中减少肿瘤发生。此外,还发现WDR43基因敲低可抑制CRC细胞中波形蛋白(VIM)的表达,而VIM的过表达可在体外和体内部分逆转WDR43的作用。

结论

总之,本研究探讨了WDR43在CRC发生发展中的作用。WDR43可能是一种有价值的生物标志物,为结直肠癌的诊断和治疗提供新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/679c1b51c217/12935_2021_2109_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/41d4db1fe30f/12935_2021_2109_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/e7de7090aa2d/12935_2021_2109_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/8def888b2e95/12935_2021_2109_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/cd4eeea658e7/12935_2021_2109_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/ee29c6a3f2c2/12935_2021_2109_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/68ca35dcb342/12935_2021_2109_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/663b81d39d0b/12935_2021_2109_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/8b1957833614/12935_2021_2109_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/679c1b51c217/12935_2021_2109_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/41d4db1fe30f/12935_2021_2109_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/e7de7090aa2d/12935_2021_2109_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/8def888b2e95/12935_2021_2109_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/cd4eeea658e7/12935_2021_2109_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/ee29c6a3f2c2/12935_2021_2109_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/68ca35dcb342/12935_2021_2109_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/663b81d39d0b/12935_2021_2109_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/8b1957833614/12935_2021_2109_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1c/8351096/679c1b51c217/12935_2021_2109_Fig9_HTML.jpg

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