MicroRNA Expression Profiling in Human Ovarian Cancer: <i>miR-214</i> Induces Cell Survival and Cisplatin Resistance by Targeting <i>PTEN</i>

Yang, Hua; Kong, William; He, Lili; Zhao, Jianjun; O'Donnell, Joshua D.; Wang, Jia-Wang; Wenham, Robert M.; Coppola, Domenico; Kruk, Patricia A.; Nicosia, Santo V.; Cheng, Jin Q.

doi:10.1158/0008-5472.can-07-2488

Cited by 981 publications

(832 citation statements)

References 31 publications

Supporting

Mentioning

795

Contrasting

Unclassified

Order By: Relevance

“…Hsa‐miR‐378 89 and let‐7i 90 are up‐regulated in patients who are sensitive to platinum; in contrast, miR‐101, 87 miR‐30c, miR‐130a and miR‐335 91 are down‐regulated in several resistant ovarian cancer cell lines, suggesting direct involvement in the development of chemoresistance. MiR‐214 induces cell survival and cisplatin resistance through targeting the 3′‐UTR of the PTEN gene, which leads to reduced expression of PTEN and activation of the Akt pathway 92. Down‐regulation of miRNA‐149 decreases the sensitivity of ovarian cancer cells to paclitaxel treatment by increasing MyD88 expression 93.…”

Section: Molecular Portraits Underlying Th Of Eocmentioning

confidence: 99%

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

Bai

Cao

Yang

et al. 2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular‐targeted therapy. Poly (ADP‐ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)‐related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

show abstract

Section: Molecular Portraits Underlying Th Of Eocmentioning

confidence: 99%

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

Bai

Cao

Yang

et al. 2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Reduced expression of miR-145 has been observed in a variety of cancers, such as colon, lung, ovarian, prostate, and breast cancer (Michael et al, 2003;Iorio et al, 2005;Yanaihara et al, 2006;Porkka et al, 2007;Yang et al, 2008). The downregulation is evident already in precancerous stages of breast and colon cancer (Michael et al, 2003;Sempere et al, 2007), suggesting loss of miR-145 as a common early neoplastic event.…”

Section: Introductionmentioning

confidence: 99%

miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

et al. 2009

View full text Add to dashboard Cite

Downregulation of miR-145 in a variety of cancers suggests a possible tumor suppressor function for this microRNA. Here, we show that miR-145 expression is reduced in bladder cancer and urothelial carcinoma in situ, compared with normal urothelium, using transcription profiling and in situ hybridization. Ectopic expression of miR-145 induced extensive apoptosis in urothelial carcinoma cell lines (T24 and SW780) as characterized by caspase activation, nuclear condensation and fragmentation, cellular shrinkage, and detachment. However, cell death also proceeded upon caspase inhibition by the pharmacological inhibitor zVAD-fmk and ectopic expression of anti-apoptotic Bcl-2, indicating the activation of an alternative caspase-independent death pathway. Microarray analysis of transcript levels in T24 cells, before the onset of cell death, showed destabilization of mRNAs enriched for miR-145 7mer target sites. Among these, direct targeting of CBFB, PPP3CA, and CLINT1 was confirmed by a luciferase reporter assay. Notably, a 22-gene signature targeted on enforced miR-145 expression in T24 cells was significantly (Po0.00003) upregulated in 55 Ta bladder tumors with concomitant reduction of miR-145. Our data indicate that reduction in miR-145 expression may provide bladder cancer cells with a selective advantage by inhibition of cell death otherwise triggered in malignant cells.

show abstract

“…It was reported that the identification of a mechanism of regulation of BCL2 expression in hematopoietic cancer cells consisted of post-transcriptional downregulation by miR-15 and miR-16 (Cimmino et al, 2005). In human ovarian cancer, aberrantly expressed miR-214 can negatively regulate PTEN by binding to its 3 0 -UTR leading to the inhibition of PTEN translation and activation of the Akt pathway (Yang et al, 2008). Expression of miR-21 was remarkably elevated in human glioblastoma and contributed to the malignant phenotype by blocking the expression of critical apoptosis-related genes (Chan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer

2009

View full text Add to dashboard Cite

Emerging evidence suggests the potential involvement of altered regulation of miRNAs in the pathogenesis of cancers, and these miRNAs are thought to be functional as tumor suppressors or oncogenes. Using miRNA arrays, we identified an miRNA differentially expressed between the MDA-MB-231 cell line and its highly metastatic variant. A bioinformatics search revealed a potential target site for miR-193b within the 3 0 UTR of uPA. Ectopic expression of miR-193b repressed the expression of sensor constructs harboring the 3 0 UTR of uPA in breast cancer cell lines. Anti-miR-193b treatment led to an increase of uPA protein and increased cell invasion in MDA-MB-231 cells. In contrast, overexpression of miR193b significantly reduced uPA protein amounts and inhibited cell invasion in MDA-MB-231 and MDA-MB-435 cells. In an immunodeficient mouse model, miR-193b significantly inhibited the growth and dissemination of xenograft tumors. Immunohistochemical staining and real-time PCR assays showed that miR-193b was a negative regulator of the uPA gene in primary breast tumors. Our research reveals that miR-193b is closely associated with clinical metastasis and identifies miR193b potentially targets uPA transcripts. Perturbation of the miRNA-mRNA pairing may have important roles in the initiation and development of breast cancer.

show abstract

MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN

Cited by 981 publications

References 31 publications

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy

miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer

Contact Info

Product

Resources

About