MicroRNA‐mediated drug resistance in ovarian cancer

Mihanfar, Aynaz; Fattahi, Amir; Nejabati, Hamid Reza

doi:10.1002/jcp.26060

Cited by 57 publications

(49 citation statements)

References 107 publications

(143 reference statements)

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“…miRNAs pair imperfectly with the 3′-untranslated region (3′UTR) of specific mRNAs to regulate the transcriptional and post-transcriptional expression of target genes (6). Mounting evidence has demonstrated that miRNAs are involved in numerous physiological and pathological processes (7,8).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

Chen

et al. 2018

Exp Ther Med

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Retinoblastoma is the most frequent intraocular malignant tumor type to occur in childhood. MicroRNA (miR)-101-3p has been reported to function as a tumor suppressor in various types of cancer. However, the biological function and underlying mechanisms of miR-101-3p in retinoblastoma are largely unknown. In the present study, it was identified that miR-101-3p was downregulated in retinoblastoma. MTT and flow cytometry assays demonstrated that ectopic overexpression of miR-101-3p significantly inhibited cell viability and cell cycle progression in WERI-Rb-1 and Y79 cells. In vivo mouse experiments further confirmed the anti-proliferative role of miR-101-3p in retinoblastoma. Additionally, predictions with TargetScan software indicated that the 3′-untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. Accordingly, a dual luciferase reporter gene assay demonstrated that miR-101-3p directly targeted EZH2 and HDAC9 to suppress the proliferation of retinoblastoma cells. Meanwhile, the restoration of EZH2 or HDAC9 expression countered the anti-proliferative effect of miR-101-3p on WERI-Rb-1 and Y79 cells. Collectively, these data highlight the role of miR-101-3p in the tumorigenesis of retinoblastoma, and indicate its suitability as a novel therapeutic target.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

Chen

et al. 2018

Exp Ther Med

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“…They play an important regulatory role in the expression of genes in both animals and plants [11]. In the case of miRNA, the regulation of gene expression takes place at the post-transcriptional level and involves interaction with mRNA [12]. The seed sequence (6-8 nucleotides) located in the 5' region of the miRNA plays a key role in this process.…”

Section: Introductionmentioning

confidence: 99%

The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs

Kaźmierczak¹,

Jopek²,

Sterzyńska³

et al. 2019

Preprint

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Ovarian cancer is the most fatal type of gynecological cancer. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. miRNA is a short noncoding RNA that regulates expression of about 60% of genes in the human genome and plays a crucial role in developing cancer, including resistance to chemotherapy.Our foremost aim was to exhibit alterations in the miRNA expression levels in the cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP) -resistant variants of W1 sensitive ovarian cancer cell line using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes.According to our observation, alterations in the expression of 40 miRNA genes. The level of expression of 21 genes was upregulated in at least one drug-resistant cell line. The expression of 19 genes was downregulated in at least one drug-resistant cell line. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ABCB1 (MDR1) gene in the W1PR1 cell line by miR-363 and regulation of the COL3A1 gene in the W1TR cell line by miR-29a.Hence, on the basis of our findings, results indicate that genes responsible for drug resistance development in ovarian cancer can be regulated by miRNA.

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“…5 Thus, drug resistance is a major clinical problem, and understanding its mechanisms and identifying its predictive biomarkers are ongoing needs. [7][8][9] Regardless of the factors, dysregulated genes are closely associated with drug resistance and prognosis in OC. [7][8][9] Regardless of the factors, dysregulated genes are closely associated with drug resistance and prognosis in OC.…”

Section: Introductionmentioning

confidence: 99%

Microarray‐based identification of genes associated with prognosis and drug resistance in ovarian cancer

Yin

Shang

Wei

et al. 2018

J of Cellular Biochemistry

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The outcome for patients with ovarian cancer (OC) is poor because of drug resistance. Therefore, identification of factors that affect drug resistance and prognosis in OC is needed. In the present study, we identified 131 genes significantly dysregulated in 90 platinum‐resistant OC tissues compared with 197 sensitive tissues, of which 30 were significantly associated with disease‐free survival (DFS; n = 16), overall survival (OS; n = 6), or both (n = 8) in 489 OC patients of the The Cancer Genome Atlas cohort. Of these 30 genes, 17 were significantly upregulated and 13 were downregulated in the 90 resistant tissues, and with one exception, all of the up‐/downregulated genes in resistant tissues were predictors of shorter DFS or/and OS. LAX1, MECOM, and PDIA4 were independent risk factors for DFS, and KLF1, SLC7A11, and PDIA4 for OS; combining these genes provided more accurate predictions for DFS and OS than any of the genes used individually. We further verified downregulation of PDIA4 protein in 51 specimens of patients with OC (24 drug resistant’s and 27 sensitive’s), which confirmed that downregulated PDIA4 predicted DFS and OS. PDIA4 also consistently predicted OS in a larger sample of 1656 patients with OC. These 30 genes, particularly the PDIA4, could be therapeutic targets or biomarkers for managing OC.

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MicroRNA‐mediated drug resistance in ovarian cancer

Cited by 57 publications

References 107 publications

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs

Microarray‐based identification of genes associated with prognosis and drug resistance in ovarian cancer

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