Project description:We performed RNAseq to study the transcriptional changes of human CAOV2 ovarian cancer cells with or without YAP silencing by siRNAs to understand the genetic determinants of ferroptosis response
Project description:We performed RNAseq to study the transcriptional changes of human CAOV2 ovarian cancer cells with or without TAZ silencing by siRNAs to understand the genetic determinants of ferroptosis response
Project description:YAP is the one of the effectors of Hippo pathway. YAP promotes organ size growth as well as tumor metastasis. In this study, YAP is silencing in clear cell carcinoma cell line RCC4 to elucidate the downstream targets that promotes the resisntance toward erastin-induced ferroptosis.
Project description:A microarray analysis was performed to compare the global gene expression profile between CLDN4-overexpressing (Control) and CLDN4-silencing SKOV-3 ovarian cancer cells.
Project description:A microarray analysis was performed to compare the global gene expression profile between CLDN4-overexpressing (Control) and CLDN4-silencing SKOV-3 ovarian cancer cells. CLDN4 gene was knocked down by CLDN4 siRNA lentivirus. Total RNA was extracted and microarray was perfomed to compare the gene profiling changes between CLDN4-overexpressing (Control) and CLDN4-silencing cells. The experiment was performed in triplicate.
Project description:Ovarian cancer is the most lethal gynecological malignancy. Recurrence and chemoresistance are tough challenges leading to poor prognosis. HJURP is a molecular chaperone of CENP-A, which is associated with aggressive progression in multiple tumors. However, the function of HJURP in ovarian cancer has not been elucidated. In our study, we found HJURP was over-expressed in ovarian cancer and high expression of HJURP was correlated to unfavorable prognosis. HJURP knockdown could inhibit proliferation, metastasis and induce G0/G1 stagnation of ovarian cancer cells. Besides, next-generation sequencing(NGS) unveiled that WEE1 was down-regulated by silencing HJURP. Further mechanistic research revealed that HJURP regulated WEE1 through MYC, and luciferase assay indicated that MYC was a transcription factor of WEE1. Additionally, we investigated that silencing HJURP increased sensitivity of ovarian cancer cells to cisplatin via MYC/WEE1 axis, and HJURP participated in DNA repair of cisplatin-induced damage. More interestingly, silencing HJURP could enhance sensitivity of ovarian cancer cells to AZD1775 and improve the synergistic effect of cisplatin plus AZD1775 combined therapy. Collectively, our data displays that HJURP promotes tumor progression and chemoresistance of ovarian cancer, and HJURP has potential to be a novel therapeutic target in the combined treatment with cisplatin and AZD1775 in ovarian cancer.
Project description:Ovarian cancer (OV) is the leading cause of mortality from gynaecological malignancies with poor prognosis and limited therapeutic options. Prevalent copy number alteration (CNA) is a genetic characteristic of OV, but its contribution to tumorigenesis remain unclear. Here, we identify RAD21, a component of the cohesin complex, as a frequently amplified and overexpressed oncogene in high grade serous ovarian cancer (HGSOC), the most common subtype of OV. RAD21 copy number amplification and overexpression are correlated with poor prognosis in HGSOC. In HGSOC cells and xenograft models, depletion of RAD21 inhibited cell proliferation by inducing mitotic phase arrest and thereby reducing tumour growth, whereas overexpression of RAD21 conferred resistance to carboplatin. Mechanistically, we found that RAD21 interacts with YAP/TEAD4 transcriptional co-repressors and recruits NuRD complex to suppress the downstream targets. Additionally, genetic and pharmacologic inhibition of YAP disrupts the co-repressor complex to suppress the oncogenic activity of RAD21 and recapitulates the phenotypes of RAD21 depletion in HGSOC. Therefore, our work sheds light on the oncogenic role of frequent CNAs and identifies a previously unrecognized role of RAD21/YAP complex which contributes to tumorigenesis and chemo-resistance in HGSOC.