MiR-204-5p/Six1 feedback loop promotes epithelial–mesenchymal transition in breast cancer

Zeng, Jun; Wei, Min; Shi, Rong; Cai, Cuixia; Liu, Xinrui; Li, Taoping; Ma, Wenxue

doi:10.1007/s13277-015-4039-1

Cited by 40 publications

(38 citation statements)

References 21 publications

(24 reference statements)

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“…Among the top 50 targets predicted by miRanda, SIX1, a transcription factor reported to be involved in the proliferation and metastasis of several cancers, stood out among the numerous candidates. SIX1 harbours a conserved miR‐204‐5p site in its 3′UTR and has been confirmed to be regulated by miR‐204‐5p in breast cancer and NSCLC . Moreover, it has been reported that SIX1 overexpression results in an acceleration in cell cycle progression that occurs as early as the G1/S transition by reactivation of cyclin‐A1 and cyclin‐D1 .…”

Section: Resultsmentioning

confidence: 96%

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miR‐204‐5p suppresses hepatocellular cancer proliferation by regulating homeoprotein SIX1 expression

Chu

Jiang

et al. 2018

FEBS Open Bio

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Fewer than 30% of patients with hepatocellular carcinoma ( HCC ) are eligible to receive curative therapies, and so a better understanding of the molecular mechanisms of HCC is needed to identify potential therapeutic targets. The role of micro RNA (mi RNA ) in modulating tumour progression has been demonstrated, and therapies targeting mi RNA appear promising. miR‐204‐5p has been shown to function in numerous types of cancer, but its role in HCC remains unclear. In this study, we found that miR‐204‐5p expression was downregulated in cancerous HCC tissues compared to nontumour tissues. Kaplan–Meier survival curve analysis also showed that low expression of miR‐204‐5p predicted worse outcomes of HCC patients. In addition, miR‐204‐5p expression was significantly lower in HCC cell lines. The function of miR‐204‐5p was also assessed both in vitro and in vivo . We demonstrated that ectopic expression of miR‐204‐5p in HCC cell lines inhibited HCC cell proliferation and clonogenicity using CCK 8, BrdU and colony‐forming assays, while the inhibition of miR‐204‐5p enhanced proliferation and clonogenicity. Further in vivo studies in mice further confirmed the proliferation capacity of miR‐204‐5p. We also identified sine oculis homeobox homologue 1 ( SIX 1 ) as a direct target of miR‐204‐5p and showed that it was inversely correlated with miR‐204‐5p in both human and mouse HCC tissues. Transfection of miR‐204‐5p mimics in BEL ‐7404 cells blocked the cell cycle by inhibiting the expression of cyclin‐D1 and cyclin‐A1, cell cycle‐related factors regulated by SIX 1. More importantly, overexpression of the 3′ UTR mutant SIX 1 but not the wild‐type SIX 1 abolished the suppressive effect of miR‐204‐5p, and downregulated SIX 1 in BEL ‐7402 cells that transfected with miR‐204 inhibitors could partly block the inhibitory effect of miR‐204‐5p on proliferation. Thus, we have demonstrated that miR‐204‐5p suppresses HCC proliferation by directly regulating SIX 1 and its downstream factors.

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Section: Resultsmentioning

confidence: 96%

“…Although miR‐204‐5p was shown to be decreased in many types of malignancy , the expression level of miR‐204‐5p in HCC tissues has not been reported. To investigate the expression level of miR‐204‐5p in HCC, we analysed the data from TCGA online data set (http://cancergenome.nih.gov/).…”

Section: Resultsmentioning

confidence: 98%

miR‐204‐5p suppresses hepatocellular cancer proliferation by regulating homeoprotein SIX1 expression

Chu

Jiang

et al. 2018

FEBS Open Bio

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“…Although most studies suggested that miR-204 is a tumor suppressor in breast cancer [20, 21, 69, 46], overexpression of miR-204 was also shown to increase migration, invasion, and metastasis of breast cancer MCF-7 cells and inhibit EMT by targeting PDEF [19]. Given that miR-204 is downregulated by androgen in MCF-7 cells (our unpublished data), it will worth examining whether the above conflicting results are caused by varied AR backgrounds in different breast cells tested.…”

Section: Physiological Functions Of Mir-204mentioning

confidence: 99%

“…However, three other positive feedback loops between miR-204 and its different targets have been established. For examples, miR-204 and its target Six1 inhibit their expression mutually [46]. TrkB-STAT3-miR-204 regulatory circuitry plays an important role in promoting metastasis in endometrial carcinoma [78].…”

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

confidence: 99%

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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“…Some of the miRNAs downregulated in DCIS are implicated in the downregulation of anti-apoptotic factors, including BCL2 (miR-143, miR195) [88,99,123], Survivin (miR-143) [89], Bcl-w (miR-497) [105] and 14-3-3f (miR-451) [103] (Table 1). In addition, these identified tumor-suppressive miRNAs also functionally target other biological processes including cell-cycle progression (Cyclin D1, targeted by miR-143) [89], angiogenesis (vascular endothelial growth factor A [VEGFA], targeted by miR-145 and miR-185) [91,96], epigenetic regulation (TET1-3, targeted by miR-22; DNA (cytosine-5)-methyltransferase 1 [DNMT1], targeted by miR-185) [79,95], Rho-dependent signal transduction (RTKN, targeted by miR-145) [92], invasion (ADP ribosylation factor 6 [ARF6], targeted by miR-145; CD147, targeted by miR-22; Six1, targeted by miR-204; Smad3, targeted by miR-489) [80,93,100,104] and degradation of the extracellular matrix (ECM) (urokinase plasminogen activator, uPA, targeted by miR-193 b) [97] (Table 1).…”

Section: Mirnas Downregulated In Dcismentioning

confidence: 99%

Noncoding RNAs in breast cancer

Lo¹,

Wolfson²,

Zhou³

et al. 2015

Briefings in Functional Genomics

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The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics.

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MiR-204-5p/Six1 feedback loop promotes epithelial–mesenchymal transition in breast cancer

Cited by 40 publications

References 21 publications

miR‐204‐5p suppresses hepatocellular cancer proliferation by regulating homeoprotein SIX1 expression

miR‐204‐5p suppresses hepatocellular cancer proliferation by regulating homeoprotein SIX1 expression

The dual regulatory role of miR-204 in cancer

Noncoding RNAs in breast cancer

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