BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

Habata, Shutaro; Iwasaki, Masanori; Sugio, Asuka; Suzuki, Miwa; Tamate, Masato; Satohisa, Seiro; Tanaka, Ryoichi; Saito, Tsuyoshi

doi:10.3892/ijo.2016.3494

Cited by 35 publications

(35 citation statements)

References 42 publications

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“…BAG3 increases the invasiveness of uterine corpus and ovarian carcinoma (35,36). Recently, there has been evidence that revealed that downregulation of BAG3 can enhance the efficacy of chemotherapeutic drugs paclitaxel in ovarian clear cell carcinoma cells (37). Induction of BAG3 expression attenuates apoptosis (38), whereas decreasing its expression promotes apoptosis in various human cell models (39).…”

Section: Discussionmentioning

confidence: 99%

Silencing of BAG3 promotes the sensitivity of ovarian cancer cells to cisplatin via inhibition of autophagy

et al. 2017

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Abstract. Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin-based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy. In the present study, as a novel autophagy regulator, BCL2-associated athanogene 3 (BAG3) was investigated to study its role in cisplatin sensitivity in epithelial ovarian cancer. However, whether BAG3 participates in cisplatin sensitivity by inducing autophagy and the underlying mechanism in ovarian cancer cells remain to be clarified. Through the use of quantitative real-time PCR, western blot analysis, CCK-8 and immunofluorescence assays our data revealed that cisplatin-induced autophagy protected ovarian cancer cells from the toxicity of the drug and that this process was regulated by BAG3. Silencing of BAG3 increased cisplatininduced apoptosis. The results also revealed BAG3 as a potential therapeutic target which enhanced the efficacy of cisplatin in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Silencing of BAG3 promotes the sensitivity of ovarian cancer cells to cisplatin via inhibition of autophagy

et al. 2017

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“…The proto‐oncogenic role of MCL1 gene in OVC has been identified by various studies during the last decade . These studies not only reported the important antiapoptotic effects of MCL1 gene on OVC but also showed that this gene had a critical function in drug resistance of OVC.…”

Section: Discussionmentioning

confidence: 98%

“…These studies not only reported the important antiapoptotic effects of MCL1 gene on OVC but also showed that this gene had a critical function in drug resistance of OVC. MCL1 protein interacts with a wide spectra of other proteins to interfere with normal cell apoptosis such as deubiquitinating enzyme 3, ubiquitin‐specific proteases, and BH3‐only protein NOXA etc . The knockdown of MCL1 gene has also been proved to be an effective way of retarding OVC cell growth.…”

Section: Discussionmentioning

confidence: 99%

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miR‐153‐3p regulates progression of ovarian carcinoma in vitro and in vivo by targeting MCL1 gene

Cui

Zhang

Zhao

et al. 2019

J of Cellular Biochemistry

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The study of either miR‐153‐3p or MCL1 gene in ovarian carcinoma (OVC) has been reported; however, the interaction between miR‐153‐3p and MCL1 gene in OVC as well as the influence of their interaction on OVC progression has not been reported yet. Herein we intended to study the effects of miR‐153‐3p/MCL1 axis in OVC. Web‐based bioinformatics algorithms including DIANA TarBase 8.0, PicTar, and TargetScan Human 7.2 were used to predict the microRNAs (miRNAs) that could target MCL1 mRNA. Patient characteristics data collection and tissue sample immunohistochemical staining were used to determine the expression level of miR‐153‐3p and MCL1. We determined to unravel the effects of the pairing‐up of miR‐153‐3p and MCL1 mRNA in OVC cell lines (OVCAR3 cell line and A2780) and xenografts (immunodeficient(immunodeficient Rag−/− mice) using several methods including real‐time quantitative reverse transcription polymerase chain reaction, westernWestern blot, colony formation assay, wound healing assay, Transwell invasion assay, flow cytometry assay, and xenograft assay. These experiments were performed to study OVC cellular activities such as cell growth and death and so forth in vitro and in vivo. Plenty of miRNAs that can target MCL1 mRNA have been identified, and we have narrowed them down to miR‐153‐3p. MCL1 gene was found overexpressed in OVC tissues and OVC cell lines at RNA and protein levels, whereas miR‐153‐3p was found under‐expressed in OVC tissues and cells. miR‐153‐3p was found to target MCL1 mRNA and interfered OVC progression. The repression of MCL1 gene expression caused by either miR‐153‐3p or small interfering RNA technique led to significantly reduced OVC cell growth and invasion in vitro. Lastly, the engraftment of transfected human OVC cells into Rag−/− mice confirmed the in vitro results. MCL1 gene acts as a cancer facilitator in OVC. In this study, we revealed the role of miR‐153‐3p on OVC progression by targeting MCL1 gene. Our work could comprehend the current understanding of OVC progression and contribute to the underlying aggression mechanism of this cancer.

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“…Mcl‐1 is a well‐defined anti‐apoptotic protein. It has been reported that increased Mcl‐1 stabilization contributes to drug resistance in ovarian cancer cells . Conversely, inhibition of Mcl‐1 can sensitize ovarian cancer cells to chemotherapeutic agents .…”

Section: Discussionmentioning

confidence: 99%

Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression

Wang

Chen

et al. 2017

J Biochem Mol Toxicol

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This study investigated the anticancer effects of geraniin on ovarian cancer cells and the signaling pathways involved. Ovarian cancer cells were treated with different concentrations of geraniin for 48 h and examined for viability, apoptosis, mitochondrial membrane depolarization, and gene expression. Xenograft tumor studies were performed to determine the anticancer activity of geraniin in vivo. Geraniin significantly decreased cancer cell viability in a concentration-dependent fashion. Geraniin significantly triggered apoptosis, which was accompanied by loss of mitochondrial membrane potential and increased cytochrome c release and caspsase-3 activity. Mechanistically, geraniin significantly downregulated Mcl-1 and impaired NF-κB p65 binding to the mcl-1 promoter. Overexpression of Mcl-1 significantly reversed geraniin-induced apoptosis in OVCAR3 cells. In addition, geraniin retarded ovarian cancer growth and reduced expression of phospho-p65 and Mcl-1. Collectively, geraniin elicits growth suppression in ovarian cancer through inhibition of NF-κB and Mcl-1 and may provide therapeutic benefits for this malignancy.

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BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer

Cited by 35 publications

References 42 publications

Silencing of BAG3 promotes the sensitivity of ovarian cancer cells to cisplatin via inhibition of autophagy

Silencing of BAG3 promotes the sensitivity of ovarian cancer cells to cisplatin via inhibition of autophagy

miR‐153‐3p regulates progression of ovarian carcinoma in vitro and in vivo by targeting MCL1 gene

Geraniin suppresses ovarian cancer growth through inhibition of NF-κB activation and downregulation of Mcl-1 expression

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