CHD1L promotes EOC cell invasiveness and metastasis via the regulation of METAP2

Abstract

Chromodomain helicase DNA binding protein 1-like (CHD1L) gene has been proposed to play an oncogenic role in human hepatocellular carcinoma. Previously we reported that CHD1L overexpression is significantly associated with the metastasis proceeding of epithelial ovarian cancer (EOC), and may predict a poor prognosis in EOC patients. However, the potential oncogenic mechanisms by which CHD1L acts in EOC remain unclear. To elucidate the oncogenic function of CHD1L, we carried out a series of in vitro assays, with effects of CHD1L ectogenic overexpression and silencing being determined in EOC cell lines (HO8910, A2780 and ES2). Real-time PCR and Western blotting analyses were used to identify potential downstream targets of CHD1L in the process of EOC invasion and metastasis. In ovarian carcinoma HO8910 cell lines, ectopic overexpression of CHD1L substantially induced the invasive and metastasis ability of the cancer cells in vitro. In contrast, knockdown of CHD1L using shRNA inhibited cell invasion in vitro in ovarian carcinoma A2780 and ES2 cell lines. We also demonstrated that methionyl aminopeptidase 2 (METAP2) was a downstream target of CHD1L in EOC, and we found a significant, positive correlation between the expression of CHD1L and METAP2 in EOC tissues (P<0.05). Our findings indicate that CHD1L plays a potential role in the inducement of EOC cancer cell invasion and/or metastasis via the regulation of METAP2 expression and suggests that CHD1L inhibition may provide a potential target for therapeutic intervention in human EOC.

A pan-cancer analysis reveals CHD1L as a prognostic and immunological biomarker in several human cancers

“…Analysis of surgical samples from 112 pancreatic cancer patients revealed that the elevation in CHD1L was positively correlated with the patients’ poor survival where the Wnt/β-catenin pathway was linked to the effect of CHD1L on tumor cells proliferation ( Liu C. et al, 2017 ). Studying the oncogenic role of CHD1L showed that it can upregulate two genes, mouse double minute two homolog (MDM2) and methionyl aminopeptidase 2 (METAP2), where the first one was associated with breast cancer progression ( Wang et al, 2019 ) and the later was linked to epithelial ovarian cancer metastasis and invasiveness ( He et al, 2020 ). CHD1L had the ability to bind to the promoter of ZKSCAN3, inhibiting its transcription and stimulating the hepatocellular carcinoma migration ( Zhang et al, 2021 ).…”

Squalene monooxygenase（SQLE) protects ovarian cancer cells from ferroptosis

“…The 5-year survival rate for EOC is 45.6% [3] and only 15.5% of patients without it. In some EOC cases, the patients may be diagnosed either too early or too late because of abnormal protein indicators [4]. Therefore, it is necessary to identify and characterize speci c proteins involved in ovarian cell death.…”

Transcriptomic Gene Network Profiling and Weak Signal Detection for Prediction of Ovarian Cancer Occurrence, Survival, and Severity by Integrating Bulk and Single-cell RNAseq Data

“…Advances in transcriptomic and genomic research have provided new insights in the discovery of OC oncogenes. Dozens of OC susceptibility genes, such as BRCA1 [5–8], BRCA2 [5–7], EPCAM [9,10] , TP53 [11,12]and CHD1L [13–15], have been identified over the past decades. However, the sensitivity and specificity using only these genes in prognostics remain suboptimal.…”