MiR-21 Upregulation Induced by Promoter Zone Histone Acetylation is Associated with Chemoresistance to Gemcitabine and Enhanced Malignancy of Pancreatic Cancer Cells

Shi, Weifeng; Wang, Lei; Huang, Weiyi; Cai, Xun; Cui, Jiujie; Wang, Liwei

doi:10.7314/apjcp.2013.14.12.7529

Cited by 37 publications

(19 citation statements)

References 53 publications

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“…35 Moreover, changes of miRNA expression profiles have been reported to be closely associated with chemotherapy effectiveness and chemotherapy drug resistance. 20,36 As an oncomiR, miR-21 has been widely reported in many cancers, but little is known about the miR-21 regulatory networks in GTD. In this study, we discovered that miR-21 was highly expressed in HM tissues and CCA cells compared with normal placental tissues and normal trophoblastic cells.…”

Section: Discussionmentioning

confidence: 99%

miR-21 Is Overexpressed in Hydatidiform Mole Tissues and Promotes Proliferation, Migration, and Invasion in Choriocarcinoma Cells

Wang

Zhao

et al. 2017

Int J Gynecol Cancer

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Section: Discussionmentioning

confidence: 99%

miR-21 Is Overexpressed in Hydatidiform Mole Tissues and Promotes Proliferation, Migration, and Invasion in Choriocarcinoma Cells

Wang

Zhao

et al. 2017

Int J Gynecol Cancer

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“…It has been shown to modulate the expression of large numbers of miRNAs in cancer cells that lead to either reduction of tumor growth or sensitization of cancer cells to chemotherapeutic agents (Sun et al, 2008;Sethi et al, 2013). miRNAs play an important role in the modulation of chemosensitivity of tumor cells (Song et al, 2013;Zhu et al, 2014). It has been reported that miR-186* is involved in curcumin-induced apoptosis in A549/ DDP multidrug-resistant human lung adenocarcinoma cells (Zhang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

Zhao¹,

Zhang²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin (10-60 μM) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

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“…The SKOV3/DDP human ovarian cancer cell line was purchased from the Affiliated Hospital of Qingdao University (Qingdao, China). The cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (both from Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), 100 U/ml penicillin and 100 µg/ml streptomycin, in a humidified cell incubator with an atmosphere of 5% CO 2 4 cells/ml SKOV3/DDP, SKOV3 or cell-free medium were seeded in a 96-well plate. Cisplatin (Qilu Pharmaceutical Co., Ltd., Jinan, China) to a concentration of 0, 3.125, 6.25, 12.5, 25, 50, 100 or 200 µmol/l was added to each well.…”

Section: Methodsmentioning

confidence: 99%

“…Multiple previous reports have indicated that dysregulation of miRNA target genes promotes drug resistance, and inhibition of miRNAs may reverse drug resistance (2,3). miRNA-21 is overexpressed in multiple types of cancer, and promotes the initiation of cancer, progression and drug-resistance (4)(5)(6)(7)(8)(9). miRNA-21 impacts tumorigenesis by negatively regulating several targets.…”

Section: Introductionmentioning

confidence: 99%

miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

Chen

Tian

et al. 2017

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are small non-coding RNAs, 8-23 nucleotides in length, which regulate gene expression at the post-transcriptional level. The present study was performed to analyze the association between microRNA-21 and cisplatin resistance in epithelial ovarian cancer (EOC) SKOV3 and SKOV3/DDP cells. In this experiment, the resistance of SKOV3 and SKOV3/DDP cells to cisplatin was evaluated using the MTT assay. Reverse transcription-quantitative polymerase chain reaction analysis was used to assess miRNA-21 levels and phosphatase and tensin homolog (PTEN) mRNA levels. Western blotting was used to assess PTEN protein levels. miRNA-21 mimics or inhibitors were transfected into SKOV3 and SKOV3/DDP cells. Prior to transfection, higher expression levels of miRNA-21 were observed in SKOV3/DDP cells compared with SKOV3 cells. Following transfection with miRNA-21 mimics, SKOV3 cells demonstrated increased sensitivity to cisplatin compared with negative control cells. Following transfection with the miRNA-21 inhibitor, SKOV3/DDP cells demonstrated decreased sensitivity to cisplatin compared with negative control cells. Furthermore, PTEN mRNA expression levels in SKOV3 cells transfected with miRNA-21 mimics was significantly lower compared with negative control cells. These results suggested that miRNA-21 may regulate cisplatin resistance by negatively targeting PTEN in EOC. IntroductionEpithelial ovarian cancer (EOC) is one of the most common malignant gynecologic tumors. Debulking surgery followed by a combination of platinum and taxane based chemotherapy are widely used treatments for EOC at present. Although overall survival rates have increased slightly over the past 25 years, 5-year survival remains <50% (1). The high mortality rate of ovarian cancer is due to late-stage diagnosis and resistance to platinum-based chemotherapy. However, the mechanisms underlying cisplatin resistance in EOC remain to be fully understood.MicroRNAs (miRNAs) are small non-coding RNAs of 8-23 nucleotides that post-transcriptionally regulate gene expression. Multiple previous reports have indicated that dysregulation of miRNA target genes promotes drug resistance, and inhibition of miRNAs may reverse drug resistance (2,3). miRNA-21 is overexpressed in multiple types of cancer, and promotes the initiation of cancer, progression and drug-resistance (4-9). miRNA-21 impacts tumorigenesis by negatively regulating several targets. Phosphatase and tensin homolog (PTEN) is a tumor suppressor molecule. Inactivating mutations and deletions of the PTEN gene have been observed in multiple types of cancer. Notably, bioinformatics tools have demonstrated that the 3'-untranslated region of the PTEN gene harbors a putative binding site for miRNA-21 (10). miRNA-21 expression has been revealed to be markedly increased in ovarian cancer compared with benign ovarian tumor tissues (11). miRNA-21 expression was also demonstrated to be increased in drug-resistant ovarian cancer compared with drug-sensitive ovarian cancer serum. In the present study,...

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MiR-21 Upregulation Induced by Promoter Zone Histone Acetylation is Associated with Chemoresistance to Gemcitabine and Enhanced Malignancy of Pancreatic Cancer Cells

Cited by 37 publications

References 53 publications

miR-21 Is Overexpressed in Hydatidiform Mole Tissues and Promotes Proliferation, Migration, and Invasion in Choriocarcinoma Cells

miR-21 Is Overexpressed in Hydatidiform Mole Tissues and Promotes Proliferation, Migration, and Invasion in Choriocarcinoma Cells

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

miRNA-21 enhances chemoresistance to cisplatin in epithelial ovarian cancer by negatively regulating PTEN

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