miR-204 mediates post-transcriptional down-regulation of PHOX2B gene expression in neuroblastoma cells

Bachetti, Tiziana; Zanni, Eleonora Di; Ravazzolo, Roberto; Ceccherini, Isabella

doi:10.1016/j.bbagrm.2015.06.008

Cited by 26 publications

(28 citation statements)

References 40 publications

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“…This provides the first evidence of miR-204’s contribution to eye disease, likely through a gain-of-function mechanism. On the other hand, the SNPs in 3′-UTR of PHOX2B differentially affect miRNA-mediated regulation of the stability of target mRNAs [41]. …”

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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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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“…Common variants have been identified in both the coding region, introns, and the 5 0 and 3 0 UTR sequences. 24,25 In agreement with the inverse correlation between effect size of mutations and their allele frequency, 26 PHOX2B causative mutations are nearly absent in unaffected individuals, while a few low frequency/ common PHOX2B variants may still have a putative mild predisposing effect toward related and rare complex diseases (see Table 1 and Figure 3), such as in the case of the involvement of polyAla contractions in Hirschsprung disease. 31 As PHOX2B mutations can be either gain or loss of function mutations, depending on the nature and position of the change, associated phenotypes may be very different.…”

Section: Phox2b Gene Variantsmentioning

confidence: 59%

“…PHOX2B overexpression in NB may be ascribed to different causes, among which the lack of miR‐204‐mediated down‐regulation of its mRNA, due to reduced miR‐204 expression in NB samples . miR‐204 has recently revealed to be a key microRNA in NB development as, in addition to PHOX2B , also MYCN has been identified among its target genes, thus suggesting an interplay among PHOX2B , miR‐204, and MYCN in this tumor.…”

Section: Phox2b Gene Variantsmentioning

confidence: 99%

“…Causative mutations can be either missense, nonsense, frameshift or in frame duplications of triplets within the 20 alanine stretch (polyAla expansions), in addition to very rare total or partial gene deletions. Common variants have been identified in both the coding region, introns, and the 5′ and 3′ UTR sequences …”

Section: Phox2b Gene Variantsmentioning

confidence: 99%

“…Moreover, PHOX2B expression in NB cell lines correlates with presence of specific 3′UTR haplotypes. Indeed, taking into consideration SNPs rs75913938, rs3833622, rs6826373, rs11723860, and rs1063611, the haplotype (g/−/g/c/a) has been found in low PHOX2B expressing cell lines whereas NB cell lines expressing high PHOX2B levels mainly carry the (g/−/g/c/T) and (g/insT/A/T/A) haplotypes . Noteworthy, the rs1063611 T allele has already been demonstrated to act as a modifier of the miR‐204‐mediated regulation of PHOX2B transcript stability …”

Section: Phox2b Gene Variantsmentioning

confidence: 99%

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Causative and common PHOX2B variants define a broad phenotypic spectrum

Bachetti

Ceccherini

2019

Clinical Genetics

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Histone deacetylase HDAC2 regulates microRNA‐125a expression in neuroblastoma

et al. 2022

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Background: Neuroblastoma (NB) is an infrequent childhood malignancy of the peripheral sympathetic nervous system and is accountable for about 10% of pediatric tumors. microRNA (miR)-125a has been implicated to serve as a tumor suppressor in various cancers. Herein, we set out to ascertain whether miR-125a exerts antitumor effects in NB.Methods: Downregulated miRNAs were identified by miRNA microarray analysis of NB tissues and paracancerous tissues. The expression of miR-125a in NB tissues and cells was detected by reverse transcription-quantitative (RT-q) PCR, followed by prognostic analysis. Gene Ontology (GO) enrichment analysis was performed on target genes of differentially expressed miRNAs. Cell proliferation, apoptosis, and differentiation were detected by cell counting kit-8 (CCK-8), Hoechst staining, immunofluorescence, and western blot. NB cells were injected into nude mice to detect tumorigenic, apoptotic, and differentiation activities in vivo. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) were carried out to verify the binding relationship between miR-125a and PHOX2B or histone deacetylases 2 (HDAC2), respectively. Finally, rescue experiments were conducted. Results: miR-125a was downregulated in NB tissues and cells, which was associated with poor prognosis. miR-125a reduced NB cell proliferation and augmented apoptosis and differentiation. NB cells with miR-125a overexpression decreased cell tumorigenesis and increased apoptosis and differentiation in xenograft tumor tissues. miR-125a targeted PHOX2B, which was highly expressed in NB tissues and cells. HDAC2, highly expressed in NB tissues and cells, repressed miR-125a transcription through histone deacetylation. Overexpression of HDAC2 or PHOX2B rescued the effects of miR-125a on NB cell proliferation, apoptosis, and differentiation. Conclusion: HDAC2 inhibited miR-125a transcription through deacetylation, and miR-125a suppressed NB development through binding to PHOX2B.

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miR-204 mediates post-transcriptional down-regulation of PHOX2B gene expression in neuroblastoma cells

Cited by 26 publications

References 40 publications

The dual regulatory role of miR-204 in cancer

The dual regulatory role of miR-204 in cancer

Causative and common PHOX2B variants define a broad phenotypic spectrum

Histone deacetylase HDAC2 regulates microRNA‐125a expression in neuroblastoma

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