PCNA‐associated factor P15<sup>PAF</sup>, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients

Jin, Chengjuan; Liu, Zhaojian; Li, Yingwei; Bu, Hualei; Wang, Yu; Xu, Ying; Qiu, Chunping; Shi, Yan; Yuan, Cunzhong; Li, Rongrong; Diao, Nannan; Zhang, Zhiwei; Wang, Xiangxiang; Liu, Lidong; Kong, Beihua

doi:10.1002/ijc.31800

Cited by 31 publications

(31 citation statements)

References 43 publications

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“…By competing with PCNA binding, KIAA0101 involves in the regulation processes of DNA replication, DNA repair, and cell cycle [4,11]. Recent researches focus on its oncogenic role and indicate that KIAA0101 level is markedly increased in various types of cancer, including breast [5], adrenal [12], ovarian [13], and gastric cancer [14]. In this study, we observed an increased expression of KIAA0101 in NSCLC tissues than in the paired normal tissues as well as in NSCLC cells.…”

Section: Discussionmentioning

confidence: 49%

“…In the tumor setting of human gastric cancer, Zhu et al reported that increased KIAA0101 was a risk marker for recurrence [14]. As for the possible mechanism behind the pro-tumor effect, KIAA0101 was reported to be involved in tumor invasion and recurrence by promoting epithelial-to-mesenchymal transition (EMT) by Zhang et al and Jin et al [13,16]. Based on the prior literature, we speculate that KIAA0101 might partly involve in EMT in NSCLC.…”

Section: Discussionmentioning

confidence: 73%

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Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

et al. 2020

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Lung cancer is the leading cause of cancer related death worldwide, with a continue-rising incidence. The proliferating cell nuclear antigen binding protein KIAA0101 is highly expressed in various types of cancer, including non-small cell lung cancer (NSCLC). However, its biological role and underlying mechanisms in NSCLC remains unclear. We downloaded KIAA0101 mRNA and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and verified the KIAA0101 expression by conducting experiments of immunochemistry (IHC), immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and western-blot. Functional experiments were performed to explore the biological roles in vitro and in vivo. The results showed that KIAA0101 was overexpressed in NSCLC tissues and cell lines. High KIAA0101 expression was associated with high T stage, nodal invasion, advanced tumor stage, and poor overall survival (P<0.01). The receiver operating characteristic (ROC) curves showed that KIAA0101 could distinguish NSCLC from paired normal tissues with statistical significance (AUC=0.969, P<0.001). The multivariate analysis revealed that KIAA0101 was an independent prognostic factor for overall survival (HR=1.249, 95% CI: 1.001-1.559, P=0.049). Furthermore, KIAA0101 knockdown induced G1 phase cell cycle arrest and inhibited NSCLC cell proliferation and migration. We also found that the depletion of KIAA0101 decreased tumor volume in nude mice. In summary, our findings suggested that KIAA0101 was a reliable diagnostic and prognostic factor in NSCLC, with potential to be a promising treatment target.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 73%

Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

et al. 2020

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“…The FOXM1 transcription factor, mainly expressed in the proliferative cells, is a member of the Forkhead box family of transcription factors. Recent studies have demonstrated that FOXM1 is frequently overexpressed in different kinds of cancers, including PCa, and is con rmed to be highly correlated with the proliferation and metastasis of many cancers [4][5][6][7][8]. Moreover, several studies indicated that FOXM1 overexpression conferred acquired chemotherapy tolerance through the regulation of many genes, including ATP-binding cassette genes [9][10], DNA damage repair genes [11], apoptosis-associated genes [12], cancer stem cell-related genes [13][14], and so on.…”

Section: Introductionmentioning

confidence: 99%

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

Yu¹,

Xu²,

wang

et al. 2020

Preprint

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Background：Resistance to docetaxel is an important factor which affects the prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), participating in cell cycle progress and cell proliferation, has been reported to affect the sensitivity of chemotherapy. The present study aims to explore the role of FOXM1 in docetaxel resistance of PCa and how FOXM1 is associated with kinesin family member 20 A (KIF20A), which has been demonstrated to promote the development of therapeutic resistance in some cancers. Methods: We monitored cell growth by MTT and colony formation assays , and cell apoptosis and cell cycle through flow cytometry. Wound-healing and transwell assays were performed to detect cell migration and invasion. The mRNA and protein expression of gene were analyzed by by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. We determined the binding of FOXM1 on the KIF20A promoter by the ChIP assay. Tumorigenicity in nude mice was employed to assess tumorigenicity in vivo. Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, and suppressed cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). The opposite trend was found in their parental cells with exogenous FOXM1 overexpression. Furthermore, thiostrepton, a specific inhibitor for FOXM1, significantly attenuated docetaxel resistance in vitro and in vivo. Additionally, we found that FOXM1 and KIF20A were consistently overexpressed and highly correlated in PCa cells and tissues. Further studies demonstrated that FOXM1 regulated the expression of KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Moreover, KIF20A overexpression could partially reverse the effects of FOXM1 depletion on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP). Conclusions: our findings suggest that highly expressed FOXM1 may promote docetaxel resistance partly through the induction of KIF20A expression and provide insights into novel chemotherapeutic strategies for docetaxel resistance in PCa.

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“…FOXM1, a transcription factor mainly expressed in proliferative cells, is part of the Forkhead box family of transcription factors. Recent studies indicate FOXM1 is commonly overexpressed in many kinds of cancers, including PCa, and its expression is highly correlated with cancer proliferation and metastasis [4][5][6][7][8]. Several studies suggest FOXM1 overexpression confers acquired chemotherapy tolerance through the regulation of numerous genes, including ATP-binding cassette genes [9][10], DNA damage repair genes [11], apoptosis-associated genes [12], cancer stem cell-related genes [13][14].…”

Section: Introductionmentioning

confidence: 99%

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

Yu¹,

Xu²,

Guo

et al. 2020

Preprint

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Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using the ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

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PCNA‐associated factor P15^PAF, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients

Cited by 31 publications

References 43 publications

Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

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PCNA‐associated factor P15PAF, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients

Cited by 31 publications

References 43 publications

Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

Overexpression of KIAA0101 Promotes the Progression of Non-small Cell Lung Cancer

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

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PCNA‐associated factor P15^PAF, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients