The Long (lncRNA) and Short (miRNA) of It: TGFβ-Mediated Control of RNA-Binding Proteins and Noncoding RNAs

Janakiraman, Harinarayanan; House, Reniqua P.; Gangaraju, Vamsi K.; Diehl, J. Alan; Howe, Philip H.; Palanisamy, Viswanathan

doi:10.1158/1541-7786.mcr-17-0547

Cited by 60 publications

(51 citation statements)

References 76 publications

(101 reference statements)

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“… 276 , 277 LncRNAs, and other noncoding RNAs such as miRNAs, work in conjunction with RNA-binding proteins (RBPs), to alter both co- and post-transcriptional gene regulation. 278 There are many cases in which, through epigenetic modifications, lncRNAs act as gene suppressors though lncRNAs may also act as gene activators. 279 , 280 MANCR (mitotically-associated noncoding RNA) is a lncRNA of particular interest, especially in its proposed association to TNBC, in the current search for therapeutic targets for its noted upregulation in breast cancer cells.…”

Section: Epigenetics and Non-coding Rnas In Breast Cancermentioning

confidence: 99%

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis

et al. 2018

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As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast. While the risk factors associated with this cancer varies with respect to other cancers, genetic predisposition, most notably mutations in BRCA1 or BRCA2 gene, is an important causative factor for this malignancy. Breast cancers can begin in different areas of the breast, such as the ducts, the lobules, or the tissue in between. Within the large group of diverse breast carcinomas, there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites. It is important to distinguish between the various subtypes because they have different prognoses and treatment implications. As there are remarkable parallels between normal development and breast cancer progression at the molecular level, it has been postulated that breast cancer may be derived from mammary cancer stem cells. Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility. Furthermore, emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer. This review provides a comprehensive survey of the molecular, cellular and genetic aspects of breast cancer.

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Section: Epigenetics and Non-coding Rnas In Breast Cancermentioning

confidence: 99%

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis

et al. 2018

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“…TGF-β signaling is regulated by miRNAs. Mechanistically, there are three types of interactions between TGF-β signaling and microRNAs: i) TGF-β regulates expressions of miRNAs, ii) miRNAs regulate the expression of genes involved in TGF-β signaling (Figure 2), and iii) miRNAs interfere with the TGF-β-induced process, such as EMT [269][270][271][272][273]. In the following chapters, we discuss the importance of these complex networks of interactions that contribute to the development and progression of genitourinary cancers, as well as responses to therapy.…”

Section: Micrornas and Tgf-β Signaling In Gcmentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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“…TGF-β signaling has many regulatory roles in development, with alterations in this signaling pathway having been associated with the pathogenesis of various diseases, including fibrotic disease, cardiovascular disease and cancer [ 14 , 15 , 16 , 17 ]. Previous studies have shown that the TGF-β signaling pathway embraces the miRNA pathway as an important component of its downstream signaling cascades [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In the present review, I summarize the connection between TGF-β signaling and miRNAs with a particular focus on: (1) regulation of miRNA expression by TGF-β signaling; (2) modulation of TGF-β signaling by miRNAs; (3) miRNA-mediated regulation of cell state transitions, such as epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT); and (4) crosstalk between miRNA and TGF-β pathways in cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Control of TGF-β Signaling

Suzuki

2018

IJMS

111

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Transcriptional and post-transcriptional regulation shapes the transcriptome and proteome changes induced by various cellular signaling cascades. MicroRNAs (miRNAs) are small regulatory RNAs that are approximately 22 nucleotides long, which direct the post-transcriptional regulation of diverse target genes and control cell states. Transforming growth factor (TGF)-β family is a multifunctional cytokine family, which plays many regulatory roles in the development and pathogenesis of diverse diseases, including fibrotic disease, cardiovascular disease and cancer. Previous studies have shown that the TGF-β pathway includes the miRNA pathway as an important component of its downstream signaling cascades. Multiple studies of epithelial–mesenchymal transition (EMT)-related miRNAs have highlighted that miRNAs constitute the intrinsic bistable molecular switches of cell states by forming double negative feedback loops with EMT-inducing transcription factors. This may be important for understanding the reversibility of EMT at the single-cell level, the presence of distinct EMT transition states and the intra- and inter-tumor heterogeneity of cancer cell phenotypes. In the present review, I summarize the connection between TGF-β signaling and the miRNA pathway, placing particular emphasis on the regulation of miRNA expression by TGF-β signaling, the modulation of TGF-β signaling by miRNAs, the miRNA-mediated modulation of EMT and endothelial–mesenchymal transition as well as the crosstalk between miRNA and TGF-β pathways in the tumor microenvironment.

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The Long (lncRNA) and Short (miRNA) of It: TGFβ-Mediated Control of RNA-Binding Proteins and Noncoding RNAs

Cited by 60 publications

References 76 publications

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis

TGF-β and microRNA Interplay in Genitourinary Cancers

MicroRNA Control of TGF-β Signaling

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