MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer

Canu, Valeria; Sacconi, Andrea; Lorenzon, Laura; Biagioni, Francesca; Sardo, Federica Lo; Diodoro, Maria Grazia; Muti, Paola; Garofalo, Alfredo; Strano, Sabrina; D’Errico, Antonietta; Grazi, Gian Luca; Cioce, Mario; Blandino, Giovanni

doi:10.18632/oncotarget.15290

Cited by 27 publications

(23 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 98%

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

Chu

Jiang

et al. 2018

FEBS Open Bio

View full text Add to dashboard Cite

show abstract

“…48 It may play a regulatory function in stem cells through targeting the CD44 and NOTCH. 49 miR-34a and miR-10b target/regulate some of stemness genes and EMT factors but with lower correlation to both pathways. The role of both miRNAs in BCSCs has been reported previously in several studies.…”

Section: Discussionmentioning

confidence: 97%

An integrated analysis to predict micro‐RNAs targeting both stemness and metastasis in breast cancer stem cells

Rahimi

Sharifi‐Zarchi

Firouzi

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Several evidences support the idea that a small population of tumour cells representing self‐renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self‐renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF‐7, MDA‐MB231, and MDA‐MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation potential, with increasing in stemness‐ and EMT‐related genes expression. Our results determined that miR‐204, ‐200c, ‐34a, and ‐10b contemporarily could target both self‐renewal and EMT pathways. This core regulatory of miRNAs could increase the survival rate of breast invasive carcinoma via up‐regulation of OCT4, SOX2, KLF4, c‐MYC, NOTCH1, SNAI1, ZEB1, and CDH2 and down‐regulation of CDH1 . The majority of those target genes were involved in the regulation of pluripotency, MAPK, WNT, Hedgehog, p53, and transforming growth factor β pathways. Hence, this study provides novel insights for targeting core regulatory of miRNAs in breast CSCs to target both self‐renewal and metastasis potential and eradication of breast cancer.

show abstract

“…MicroRNAs (miRNAs/miRs) are a type of non-coding RNA (18–24 nucleotides in length) that regulate mRNA expression by binding to the 3′untranslated regions (UTR) of target mRNAs ( 3 ). Increasingly, evidence has revealed that miR-204 is downregulated in breast cancer ( 4 ), glioma ( 5 ), gastric cancer ( 6 ) and acute myeloid leukemia ( 7 ). However, to the best of our knowledge, no information is available regarding the function of miR-204 in HNSCC progression.…”

Section: Introductionmentioning

confidence: 99%

miR‑204 enhances p27 mRNA stability by targeting Brd4 in head and neck squamous cell carcinoma

Wang

Zhang

Zhou³

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

The present study aimed to explore the function of microRNA (miR)-204 in modulating cyclin-dependent kinase inhibitor 1B (p27) mRNA stability in head and neck squamous cell carcinoma (HNSCC). Briefly, reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect miR-204 and Brd4 level. Cell viability, cell cycle and cell apoptosis were used to investigate the effects of miR-204. Additional luciferase reporter and mRNA stability assays were used to explore the mechanisms contributing to miR-204 effects. Here, miR-204 was downregulated in HNSCC tissues compared with the adjacent normal tissues. The expression levels of miR-204 and bromodomain-containing protein 4 (Brd4) were negatively associated in HNSCC tissues. Ectopic expression of miR-204 inhibited HNSCC cell proliferation, promoted cell cycle arrest at the G1/S phase and promoted cell apoptosis compared with control cells. Additionally, upregulation of miR-204 expression levels enhanced p27 mRNA stability. Notably, Brd4 was identified as a target of miR-204, and the co-expression of Brd4 with miR-204 mimics attenuated the inhibitory effects of miR-204 on cell proliferation and enhanced p27 mRNA stability compared with control cells. Thus, it was concluded that miR-204 functions as a tumor suppressor by enhancing p27 mRNA stability through targeting Brd4 in HNSCC.

show abstract

MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer

Cited by 27 publications

References 31 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

An integrated analysis to predict micro‐RNAs targeting both stemness and metastasis in breast cancer stem cells

miR‑204 enhances p27 mRNA stability by targeting Brd4 in head and neck squamous cell carcinoma

Contact Info

Product

Resources

About