nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

Abstract

Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.

Protein kinase R and its cellular regulators in cancer: An active player or a surveillant?

“…nc886 has a strong CpG island at the promoter region and its expression is silenced in a subset of malignant cells by DNA hypermethylation at the CpG island (Park et al, ). nc886 silencing occurs frequently in a number of malignancies (Ahn et al, ; Cao et al, ; Fort et al, ; Lee, Lee, et al, ; Lee, Park, et al, ; Park et al, ; Treppendahl et al, ), presumably because nc886 is an imprinted gene (Carpenter et al, ; Paliwal et al, ; Romanelli et al, ). Unlike typical imprinted genes which show monoallelic methylation in 100% of individuals, nc886 is estimated to be methylated in the maternal allele in approximately 75% of individuals (Treppendahl et al, ).…”

Up‐regulation of paired‐related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a

“…Cultured cardiac fibroblasts were infected with adenovirus expressing negative control (NC) shRNA or Prrx2 shRNA for 48 h and then treated with TGF-β (10 ng/ mL) for 24 h. A, Cell differentiation was determined by immunofluorescence analysis of α-SMA and quantitative analysis was shown. [41][42][43] Thus, we reasoned that TGF-β may increase Prrx2 expression via the specific miR. C and D, Total cell lysates of cardiac fibroblasts were subjected to perform Western blotting analysis to detect protein levels of α-SMA, p-ERK, p-JNK, Col I, and Col III in C and quantitative analysis was performed in D. N is 5 in each group.…”

“…40 Interestingly, TGF-β up-regulates multiple microRNAs to produce its biological actions such as miR-124 and miR-101 as epigenetic factors. [41][42][43] Thus, we reasoned that TGF-β may increase Prrx2 expression via the specific miR.…”

Comprehensive analysis of mRNA‐level and miRNA‐level subpathway activities for identifying robust ovarian cancer prognostic signatures

“…Through binding to 3'‐untranslated regions of messenger RNAs (mRNAs) or other RNAs, miRNAs display crucial regulatory roles at the post‐transcriptional level . MiRNA‐related pathways play an important role in reprogramming mRNA expression in OvCa . Givel et al verified that the regulatory function of miR‐200 on CXCL12β could affect immuno‐suppression and fibroblast heterogeneity in OvCa .…”

“…4 MiRNA-related pathways play an important role in reprogramming mRNA expression in OvCa. 5 Givel et al verified that the regulatory function of miR-200 on CXCL12β could affect immuno-suppression and fibroblast heterogeneity in OvCa. 6 Bagnoli et al identified a miRNA-based signature (MiROvaR) to successfully predict early relapse and progression of epithelial OvCa.…”