Interfering EZH2 Expression Reverses the Cisplatin Resistance in Human Ovarian Cancer by Inhibiting Autophagy

Sun, Yang; Jin, Long; Liu, Jiahua; Sui, Yuxia; Han, Lili; Shen, Xiaoli

doi:10.1089/cbr.2016.2034

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…Patients with ovarian cancer usually respond well to initial chemotherapy with cisplatin. However, most patients develop resistance to cisplatin during the course of their treatment ( 1 , 19 ). Hence, there is an urgent need to identify new therapeutic targets in ovarian cancer and to develop novel, potent and specific drugs.…”

Section: Discussionmentioning

confidence: 99%

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

Ling

et al. 2017

Oncology Reports

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The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p-p53-Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

Ling

et al. 2017

Oncology Reports

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“…The effects of miR-31 on the efficacy of platinum compounds have been discussed extensively. It has been shown that the expression levels of miR-31 are negatively correlated with E2F transcription factor 2 (E2F2) and Enhancer of zeste homolog 2 (EZH2) in malignant tumors including gastric, ovarian and bladder cancer, and CRC (37)(38)(39)(40)(41). E2F2 and EZH2 can enhance drug resistance by inhibiting platinum-drug-mediated apoptosis, whereas low expression levels of E2F2 and EZH2 enhance platinum chemosensitivity (39,(42)(43)(44)(45).…”

Section: Os ---------------------------------------------------------mentioning

confidence: 99%

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

Xin

et al. 2018

Oncol Rep

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The expression levels of microRNA‑31 (miR‑31) and LOC554202 have been previously investigated in colorectal cancer (CRC) and their oncogenic and/or tumor suppressive roles have been described. The aim of the present study was to examine the role of miR‑31 and its host gene LOC554202 in the prognosis of patients with CRC. Patients with CRC treated with oxaliplatin‑based chemotherapy between June 2005 and March 2010 were recruited to the First Affiliated Hospital of China Medical University. Tumor and adjacent mucosal tissues were collected. The detection of miR‑31 and/or LOC554202 was performed with probe hybridization targeting. Correlation analysis was performed among the expression levels of miR‑31, LOC554202, and their association with clinicopathological parameters and/or survival rates. miR‑31 and LOC554202 were expressed at high levels in CRC (P<0.01) compared with adjacent intestinal mucosa. A linear correlation was noted for the two markers in CRC tissues (P<0.01). The expression of miR‑31 was significantly higher in adenocarcinoma than in the adjacent intestinal mucosa (P<0.01), whereas the expression of LOC554202 was significantly higher in the adenocarcinoma and the rectal cancer tissue regions (P<0.01). The high expression levels of miR‑31 and LOC554202 were associated with high disease‑free survival (DFS) and overall survival (OS) rates (P<0.05). Associations between the increase in DFS and OS and the elevated expression levels of miR‑31 and LOC554202 were present in patients with colon cancer but not in patients with rectal cancer (P<0.05). These data indicated that miR‑31 and LOC554202 may be potential markers for evaluation of the prognosis of patients treated with oxaliplatin‑based chemotherapy.

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“…Overexpressed PDA/PD-L1 not only decreased immunotherapy efficiency, but also increased lung cancer resistance to cisplatin [ 12 ]. In human ovarian cancer, upregulated zeste homolog 2 (EZH2) resulted in cisplatin by promoting cyclin-dependent kinases (CDK1, CDK2) and H3K27me3 [ 13 ]. In bladder cancer cells, the long non-coding RNA UCA1 increased cisplatin resistance by promoting microRNA (miR)-196a-5p expression targeting p27 kip1 [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

WP1130 attenuates cisplatin resistance by decreasing P53 expression in non-small cell lung carcinomas

et al. 2017

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Cisplatin-based combination chemotherapy significantly improves the survival outcomes in non–small cell lung carcinomas (NSCLCs), but drug resistance commonly contributes to disease progression and relapse. Recently, accumulating evidence has indicated that deubiquitinases (DUBs) are involved in regulating tumor cell proliferation, apoptosis, and chemoresistance. We designed this study to investigate the role of WP1130, a DUB inhibitor, in regulating cisplatin cytotoxicity in NSCLCs. After being combined with WP1130, cisplatin sensitivity was significantly increased in A549 and HCC827 cells with decreased p53 expression, inhibiting their proliferation, but not in p53-deficient NCI-H1299 cells. The synergistic cytotoxicity of the cisplatin and WP1130 co-treatment was abolished in p53-knockdown cells. Western blotting verified the decreased p53 expression in A549 and HCC827 cells treated with cisplatin and WP1130. The administration of MG132, a proteasome inhibitor, or knockdown of ubiquitin-specific peptidase 9, X-linked (USP9X) both eliminated the effect of WP1130 in decreasing p53 expression. Taken together, our findings confirm that the inclusion of WP1130 is potentially contributes to better therapeutic effects of cisplatin-based chemotherapy of NSCLCs in a manner dependent on the USP9X–p53 ubiquitination–mediated degradation pathway.

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Interfering EZH2 Expression Reverses the Cisplatin Resistance in Human Ovarian Cancer by Inhibiting Autophagy

Cited by 23 publications

References 19 publications

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

High expression of microRNA‑31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin

WP1130 attenuates cisplatin resistance by decreasing P53 expression in non-small cell lung carcinomas

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