Upregulation of miR‐23a∼27a∼24 decreases transforming growth factor‐beta‐induced tumor‐suppressive activities in human hepatocellular carcinoma cells

Huang, Shenglin; He, Xianghuo; Ding, Jie; Liang, Linhui; Zhao, Yingjun; Zhang, Zhenfeng; Xiao, Yao; Pan, Zhifang; Zhang, Pingping; Li, Jinjun; Wan, Dafang; Gu, Jianren

doi:10.1002/ijc.23580

Cited by 207 publications

(175 citation statements)

References 24 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the results support the possibility that the accumulation of these miRs is intended to protect ESCs from an inappropriate apoptosis induced by BMP4. The anti-apoptotic role of these miRs was already described in other experimental systems [32][33][34] and was also confirmed in our experiments where ESCs were exposed to genotoxic stress (Figure 4e). However, the mechanism through which the miRs exert this function is not clearly understood.…”

Section: Discussionsupporting

confidence: 90%

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

et al. 2014

View full text Add to dashboard Cite

Numerous studies have indicated that BMP4 signaling is involved in the regulation of the early steps of development. In mouse embryonic stem cells (ESCs), BMP4 is crucial to sustain pluripotency and blocks differentiation towards neural fate. Here, through a systematic analysis of miRNAs in ESCs, we establish that BMP4 signaling regulates miR-23a, 27a and 24-2, through the recruitment of phospho-Smads at the promoter of the gene encoding this miRNA cluster. Suppression of miR-23a/b, 27a/b and 24 does not affect self-renewal or pluripotency, but induces an evident change of ESC differentiation, with a significant increase of the cells undergoing apoptosis after the transition from ESCs to epiblast stem cells (EpiSCs). BMP4 has been previously reported to cause apoptosis during ESC differentiation. By blocking BMP4 signaling, we completely prevent the apoptosis induced by suppression of the miRs. This suggests that the effects of miR suppression are the result of enhanced BMP4 signaling. This hypothesis is further supported by the observation that Smad5, the transcription factor downstream of the BMP4 receptor, is targeted by the miRNAs of the 23a and 23b clusters. Altogether, our results highlight the existence of a regulatory loop, involving Smad5 and the miR-23a clusters, that modulates the apoptotic response of ESCs to BMP4. Cell Death and Differentiation (2015) 22, 1047-1057 doi:10.1038/cdd.2014; published online 5 December 2014ESCs represent a precious experimental model of the early stages of embryo development. They can be grown indefinitely in vitro and induced to differentiate, thus mimicking two events taking place in the blastocyst: (i) the differentiation of the cells of the inner cell mass into epiblast cells and (ii) the commitment of epiblast cells to neuroectodermal or mesendodermal precursors. 1,2 These differentiation events are regulated by extrinsic signals. BMP4, a member of the TGF-β superfamily of cytokines, has a crucial role in ESCs. Many results indicate that it is able, together with LIF, to maintain mouse ESCs in the pluripotent state. 3 This effect is mediated by the regulation of many direct targets of Smad1, 5 and 8, the transcription factors downstream of the BMP4 receptor. 4 BMP4 also contributes to govern early steps of differentiation. First, BMP4 acts by regulating ESC-epiblast transition and then by suppressing neural differentiation and promoting non-neural lineage formation. 2 Moreover, BMP4 promotes the differentiation towards mesendodermal lineages and also regulates, either positively or negatively, the further commitment of mesendodermal precursors into their different fates. [5][6][7][8] Gene expression in ESCs is regulated by a complex network of transcription factors. 9,10 In addition, numerous results indicate that miRNAs are crucial regulators of the gene expression programs that drive ESC differentiation. Suppression of miRNA biogenesis, obtained by knocking out Dicer or DCGR8 genes, leads to an early arrest of mouse embryonic development and of in vitro differenti...

show abstract

Section: Discussionsupporting

confidence: 90%

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that miR-27a contributes to the transformation or maintenance of a malignant state in breast cancer cells or gastric adenocarcinoma by targeting mRNAs of the transcription factor FOXO1 (Guttilla and White, 2009) and the membrane protein prohibitin (Liu et al, 2009). In hepatocellular carcinoma cells, upregulation of miR-27a confers the cells resistant to apoptosis induced by transforming growth factor-b (Huang et al, 2008). Moreover, miR-27a modulates the malignant biological behavior of pancreatic cancer cells by targeting sprouty2 mRNA, a crucial molecule involved in the Ras/MAPK signaling pathway (Ma et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen

Wang

et al. 2011

Oncogene

View full text Add to dashboard Cite

“…In addition, miR-128 inhibits glioma cell proliferation by targeting the transcription factor, E2F3a (13), and miR-200c and miR-141 (members of the miR-200 family) are important regulators of the epithelial to mesenchymal transition in normal and cancer cells (7,14). Furthermore, fragments of miRNA can be found and measured in the serum of patients with cancer, and could potentially act as a novel class of biomarkers for diagnosis or cancer staging; for instance, tumor-suppressive activities in human hepatocellular carcinoma cells are decreased by up-regulation of miR23a~27a~24 (15). However, the complexity of the structures and cloning processes for miRNAs has prevented the analysis of large numbers of clinical samples.…”

Section: Introductionmentioning

confidence: 99%

microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein

Zhang

Liu

Huang³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Lung cancer is one of the main causes of cancer death worldwide. The cortactin gene, CTTN, may play a pivotal role in the proliferation and invasion of tumors. A microRNA (miR-182) was cloned and used to study the expression of CTTN and its regulatory effects on the proliferation and invasion of the lung cancer cell line, A549. cortactin protein and CTTN mRNA expression decreased in A549 cells that were transfected with the miR-182 expression plasmid. A cell proliferation assay indicated that miR-182 expression affected cell cycle regulation and suppressed proliferation of lung cancer cells in vitro. In addition, xenograft experiments confirmed the suppression of tumor growth in vivo, which was due to the promotion of apoptosis. In conclusion, endogenous mature miR-182 expression may have an important role in the pathogenesis of lung cancer through its interference with the target gene CTTN by epigenetic modification.

show abstract

Upregulation of miR‐23a∼27a∼24 decreases transforming growth factor‐beta‐induced tumor‐suppressive activities in human hepatocellular carcinoma cells

Cited by 207 publications

References 24 publications

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis

Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen

microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein

Contact Info

Product

Resources

About