WD repeat domain 62 (WDR62) promotes resistance of colorectal cancer to oxaliplatin through modulating mitogen-activated protein kinase (MAPK) signaling

ABSTRACT

WD repeat domain 62 (WDR62) is involved in embryonic brain growth through regulation of glial and neural cell populations. WDR62 is also implicated in the carcinogenesis of various cancers. The role of WDR62 in progression and chemoresistance of colorectal cancer (CRC) was investigated. Firstly, oxaliplatin-resistant CRC cells (HCT116/R and HT29/R) were sequentially exposed to an increasing concentration of oxaliplatin. The results showed that WDR62 was elevated in CRC tissues, and oxaliplatin resistance conferred up-regulation of WDR62 in CRC cells. Knockdown of WDR62 reduced cell proliferation and promoted the apoptosis of oxaliplatin-resistant CRC cells. Moreover, silencing of WDR62 increased fluorescence intensity of γH2AX, and decreased protein expression of p-DNA-PK and Rad51 in the oxaliplatin-resistant CRC cells. The protein expression of p-ERK, p-JNK, and p-p38 in oxaliplatin-resistant CRC cells were down-regulated by knockdown of WDR62. In conclusion, silencing of WDR62 suppressed oxaliplatin resistance and DNA damage repair of CRC cells through inactivation of MAPK signaling.

graphica abstract

KEYWORDS:

• WDR62
• oxaliplatin resistance
• proliferation
• apoptosis
• DNA damage repair
• colorectal cancer
• MAPK

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contribution of authors

Juanjuan Cai designed the experiments and Lingling Su carried them out. Weiwei Luo analyzed and interpreted the data, prepared the manuscript with contributions from all co-authors.

Ethics approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Data availability

The authors declare that all data supporting the findings of this study are available within the paper and any raw data can be obtained from the corresponding author upon request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21655979.2022.2086381

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.