Detection of MicroRNA as Novel Biomarkers of Epithelial Ovarian Cancer From the Serum of Ovarian Cancer Patient

Chung, Youn Wook; Bae, Hyo Sook; Song, Jae Yun; Lee, Jae Kwan; Lee, Nak Woo; Kim, T.; Lee, Kyu Wan

doi:10.1097/igc.0b013e31828c166d

Cited by 126 publications

(85 citation statements)

References 26 publications

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“…miR-145, located at 5q32, was found to be decreased in various types of cancers such as breast, 13 colon, 14,15 lung, 16 liver, 17 bladder, 18 pituitary, 19 B cell, 20 ovary 4,14,21 and prostate. 22 To date, a cohort of genes related to different cancer pathways have been identified as its target genes.…”

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confidence: 99%

Expression of Concern: miR‐145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6

Zhu

Xie

et al. 2014

Intl Journal of Cancer

104

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Multidrug resistance (MDR) remains a major obstacle to effective chemotherapy treatment in ovarian cancer. In our study, paclitaxel-resistant ovarian cancer patients and cell lines had decreased miR-145 levels and expressed high levels of Sp1 and Cdk6. Introducing miR-145 into SKOV3/PTX and A2780/PTX cells led to a reduction in Cdk6 and Sp1 along with downregulation of P-gp and pRb. These changes resulted in increased accumulation of antineoplastic drugs and G1 cell cycle arrest, which rendered the cells more sensitive to paclitaxel in vitro and in vivo. These effects could be reversed by reintroducing Sp1 or Cdk6 into cells expressing high levels of miR-145, resulting in restoration of P-gp and pRb levels. Furthermore, we confirmed that both Cdk6 and Sp1 are targets of miR-145. Intriguingly, demethylation with 5-aza-dC led to reactivation of miR-145 expression in drug-resistant ovarian cancer cell lines, which also resulted in increased sensitivity to paclitaxel. Collectively, these findings begin to elucidate the role of miR-145 as an important regulator of chemoresistance in ovarian cancer by controlling both Cdk6 and Sp1.Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Because of the absence of early symptoms, most patients are diagnosed at an advanced stage. Chemotherapy is one of the most frequently used treatment modalities for advanced-stage ovarian cancer patients. Although initial responsiveness to first-line chemotherapy consisting of a platinum-containing compound in combination with paclitaxel (PTX) is high, up to 80% of patients eventually relapse and become platinum/taxane resistant. Therefore, a better understanding of the mechanisms involved in MDR ovarian cancer and more effective therapeutic approaches are immediately required.1 Multiple mechanisms that mediate intrinsic or acquired resistance to paclitaxel have been identified. A major contributor to resistance is the active export of drugs by transmembrane polysubstrate efflux pumps that prevent drugs from reaching their intracellular targets, and a highly studied member of this family is multidrug resistance-1 (MDR1). MDR1 encodes for the membrane transporter P-glycoprotein (P-gp), whose substrates included a wide array of toxins and commonly used chemotherapeutic agents, including taxanes and anthracyclines. 2 Cell cycle dysregulation is another common molecular finding in ovarian cancer, and the cyclin-dependent kinases (Cdks) represent attractive targets in this pathway. For example, inhibition of Cdk6, one of the powerful cell cycle progression regulators, showed encouraging effects in animal experiments and clinical trials. MicroRNAs (miRNAs) are small, noncoding RNA molecules that negatively regulate a large number of proteinencoding genes via either mRNA degradation or translational silencing. Evidence is emerging for roles of miRNAs in modulating drug sensitivity/resistance of cells, 4,5 specifically for one class of miRNAs that target survival pathways or pathways that regulate apoptosis sensitivity, such ...

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confidence: 99%

Expression of Concern: miR‐145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6

Zhu

Xie

et al. 2014

Intl Journal of Cancer

104

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“…The expression of circulating miRNA precursor let-7b was reported to be diverse among various cancer types. Let-7b was found to be upregulated in breast tumors (29) and downregulated in ovarian cancer (30). The same trend was found for the expression of circulating let-7c, which was increased in esophageal cancer (31) but decreased in nasopharyngeal carcinoma patients with poor prognosis (32).…”

Section: Discussionsupporting

confidence: 58%

226 Identification of circulating microRNA signatures for upper tract urothelial carcinoma detection

Tang¹,

Pengchao²,

Chao³

et al. 2015

European Urology Supplements

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“…An increasing number of studies have revealed the vital role microRNAs play in ovarian cancer carcinogenesis [14][15][16][17][18][19][20][21]. However, Most of these studies have been performed on ovarian tissue samples.…”

Section: Introductionmentioning

confidence: 99%

A novel serum microRNA panel to discriminate benign from malignant ovarian disease

et al. 2015

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Detection of MicroRNA as Novel Biomarkers of Epithelial Ovarian Cancer From the Serum of Ovarian Cancer Patient

Abstract: Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer. Also, serum miRNAs is a promising and useful tool for discriminating between controls and patients with serous ovarian cancer.

Cited by 126 publications

References 26 publications

Expression of Concern: miR‐145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6

Expression of Concern: miR‐145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6

226 Identification of circulating microRNA signatures for upper tract urothelial carcinoma detection

A novel serum microRNA panel to discriminate benign from malignant ovarian disease

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