Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3′ UTR of BCL2 mRNA

Kuwano, Yuki; Nishida, Kensei; Kajita, Keisuke; Satake, Yuzuru; Akaike, Yoko; Fujita, Kinuyo; Kano, Shizuka; Masuda, Kiyoshi; Rokutan, Kazuhito

doi:10.1038/cdd.2014.176

Cited by 58 publications

(52 citation statements)

References 46 publications

(50 reference statements)

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“…However, none of the studies thus far revealed the presence of inverse correlation between expression of BCL-2 and miR-204 [24–27]. Given that a mechanism blocking the binding of miR-204 to 3′-UTR of BCL-2 was recently proposed [54] (also shown later), a further study is needed to confirm that miR-204 is actually the key regulator of BCL-2 in vivo . …”

Section: Physiological Functions Of Mir-204mentioning

confidence: 99%

“…Besides some SNPs, human transformer 2β (TRA2β) has been recently reported to affect interaction of miR-204 and its target by competing the binding sequence of miR-204 in a mutually exclusive way [54]. TRA2β is a serine/arginine-rich-like protein splicing factor with wide-ranging roles in gene expression as an RNA-binding protein.…”

Section: Factors Regulating Expression and Function Of Mir-204mentioning

confidence: 99%

“…TRA2β is a serine/arginine-rich-like protein splicing factor with wide-ranging roles in gene expression as an RNA-binding protein. The consensus sequence for TRA2β-binding (GAA) lies within the miR-204-binding site of BCL-2 3′-UTR, TRA2β antagonizes the effects of miR-204 and upregulates BCL-2 expression [54]. Such a mechanism is very interesting, partially because it can explain why miR-204 regulates expression of its targets with different efficiencies in the way depending on cell lines used [44].…”

Section: Factors Regulating Expression and Function Of Mir-204mentioning

confidence: 99%

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The dual regulatory role of miR-204 in cancer

Pan

2016

Tumor Biol.

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MicroRNAs (miRNAs) are a group of endogenous, small (about 22 nucleotides) non-coding RNAs which negatively regulate gene expressions. As one of them, miR-204 originates from the sixth intron of the transient receptor potential melastatin 3 (TRPM3) gene. Therefore, expression of miR-204 is under the control of the TRPM3 promoter and regulated by genetic and epigenetic mechanisms. miR-204 has been found to play the important roles in development of eyes and adipogenesis. Its pathological functions have been observed in a few diseases including pulmonary arterial hypertension, diabetes, and various types of cancers. It is believed that miR-204 acts as a tumor-suppressor via promoting apoptosis, conferring the resistance of cancer cells to chemotherapy, and suppressing the self-renewal of cancer stem cells (CSCs) and the epithelial to mesenchymal transition (EMT). Expression of miR-204 is repressed by its targets XRN1 and TRKB in prostate cancer and endometrial carcinoma, respectively; therefore, they establish an oncogenic feedback loops that play an important role promoting development of cancer. In this review, we summarize our current knowledge regarding miR-204, including its expression, regulation and biological functions, especially focusing our discussion on its role in tumor development and tumor progression.

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Section: Physiological Functions Of Mir-204mentioning

confidence: 99%

Section: Factors Regulating Expression and Function Of Mir-204mentioning

confidence: 99%

Section: Factors Regulating Expression and Function Of Mir-204mentioning

confidence: 99%

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The dual regulatory role of miR-204 in cancer

Pan

2016

Tumor Biol.

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“…TRA2β also regulates splicing of the estrogen receptor α, decreasing the expression of the ERaΔ7 isoform, which correlates with a better outcome in endometrial cancer (Hirschfeld et al 2015). Finally, TRA2β regulates turnover of BCL2 mRNA, in a splicing-independent fashion, by competing with miR-204 for binding to the 3 ′ UTR (Kuwano et al 2015).…”

Section: Tra2β-transformer 2β Homolog (Drosophila)mentioning

confidence: 99%

Splicing-factor alterations in cancers

Anczuków

Krainer

2016

RNA

217

230

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Tumor-associated alterations in RNA splicing result either from mutations in splicing-regulatory elements or changes in components of the splicing machinery. This review summarizes our current understanding of the role of splicing-factor alterations in human cancers. We describe splicing-factor alterations detected in human tumors and the resulting changes in splicing, highlighting cell-type-specific similarities and differences. We review the mechanisms of splicing-factor regulation in normal and cancer cells. Finally, we summarize recent efforts to develop novel cancer therapies, based on targeting either the oncogenic splicing events or their upstream splicing regulators.

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“…Links have been found between miRNAs and numerous developmental and pathological processes [13,15] . In particular, miR-204 and miR-211 belong to the same miRNA sub-family and share the same seed sequence: miR-204 is embedded in intron 6 of the TRPM3 gene (transient receptor potential melastatin 3) and has been shown to be a key regulator in metabolism, cell death, and cardiovascular disease [16][17][18][19][20] , and miR-211 is encoded by intron 6 of the TRPM1 gene [17,21] and also been shown to play important roles in cell survival and cancer [22][23][24] . miR-204 is completely conserved between human and mouse.…”

Section: Introductionmentioning

confidence: 99%

Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells

et al. 2015

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Aim:The mitochondrial targeted 2C-type serine/threonine protein phosphatase (PP2Cm) is encoded by the gene PPM1K and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. Its expression is dynamically regulated by the nutrient environment and pathological stresses. However, little is known about the molecular mechanism underlying the regulation of PPM1K gene expression. In this study, we aimed to reveal how PPM1K expression is affected by miRNA-mediated post-transcriptional regulation. Methods: Computational analysis based on conserved miRNA binding motifs was applied to predict the candidate miRNAs that potentially affect PPM1K expression. Dual-luciferase reporter assay was performed to verify the miRNAs' binding sites in the PPM1K gene and their influence on PPM1K 3'UTR activity. We further over-expressed the mimics of these miRNAs in human and mouse cells to examine whether miRNAs affected the mRNA level of PPM1K. Results: Computational analysis identified numerous miRNAs potentially targeting PPM1K. Luciferase reporter assays demonstrated that the 3'UTR of PPM1K gene contained the recognition sites of miR-204 and miR-211. Overexpression of these miRNAs in human and mouse cells diminished the 3'UTR activity and the endogenous mRNA level of PPM1K. However, the miR-22 binding site was found only in human and not mouse PPM1K 3'UTR. Accordingly, PPM1K 3'UTR activity was suppressed by miR-22 overexpression in human but not mouse cells. Conclusion: These data suggest that different miRNAs contribute to the regulation of PP2Cm expression in a species-specific manner. miR-204 and miR-211 are efficient in both mouse and human cells, while miR-22 regulates PP2Cm expression only in human cells.

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Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3′ UTR of BCL2 mRNA

Cited by 58 publications

References 46 publications

The dual regulatory role of miR-204 in cancer

The dual regulatory role of miR-204 in cancer

Splicing-factor alterations in cancers

Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells

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