The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells

Wang, Lina; Chen, Weiwen; Zhang, Ju; Li, Chaoyang; Liu, Chunyan; Xue, Jing; Zhang, Pengju; An-li, Jiang

doi:10.1038/aja.2013.84

Cited by 17 publications

(14 citation statements)

References 28 publications

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“…In NSCLC cell lines, let-7a inhibits cell proliferation and invasion by interacting with K-Ras and HMGA2 [ 104 ]. Target analysis reveals that IGF1R is a target gene, one of let-7's numerous targets, and is involved in the IGF1R/RAS/MAPK/ELK1 pathway, playing major roles in cell proliferation and cell survival [ 109 ]. In ovarian cancer, it was reported that let-7e has many target genes including HMGA2, C14ofr28, LIN28B, and ARID3B, and let-7e expression is lower than in adjacent tissues [ 110 ].…”

Section: Resultsmentioning

confidence: 99%

Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

Huang

Jing

Cai

2015

BioMed Research International

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The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network. Then, we isolated the lung cancer subnetwork by identifying the known lung cancer genes and their direct regulators. This subnetwork was refined by the Bayesian method, and the directed regulations among mRNA genes, microRNAs, methylations, and CNVs were obtained. The novel candidate key drivers in this refined subnetwork, such as the methylation of ARHGDIB and HOXD3, microRNA let-7a and miR-31, and the CNV of AGAP2, were identified and analyzed. On three large public available lung cancer datasets, the key drivers ARHGDIB and HOXD3 demonstrated significant associations with the overall survival of lung cancer patients. Our results provide new insights into lung cancer mechanisms.

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Section: Resultsmentioning

confidence: 99%

Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

Huang

Jing

Cai

2015

BioMed Research International

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“…Interestingly, bioinformatics approaches have predicted onethird of all mammalian genes to be targeted and regulated by miRNAs [25][26][27]. Previous studies have shown that aberrant miRNA expression could impact normal biological processes, resulting in PC initiation and progression [28][29][30]. However, a role of miR-323 in the carcinogenesis of PC has not been studied.…”

Section: Introductionmentioning

confidence: 99%

MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor

Gao

Yao

Zheng

2015

Cell Physiol Biochem

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Background/Aims: The current treatments fail to provide satisfactory cure for aggressive prostate cancers (PCs). Hence, further comprehension of PC metastasis is highly appreciated for improving the levels of therapy. We have previously shown that Adiponectin reduces the levels of vascular endothelial growth factor A (VEGF-A) in PCs to suppress tumor-associated neovascularization, possibly through AMPK/mTor signaling. Here, we studied the regulation of Adiponectin signaling in PCs. Methods: We analyzed the levels and correlation of Adiponectin receptor 1 (AdipoR1) and microRNA-323 (miR-323) in the PC specimen, compared to the paired normal prostate tissue. We analyzed the binding of miR-323 to the 3'UTR of AdipoR1 mRNA and its effects on AdipoR1 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-323 levels in PC cells, and examined the effects on the expression of AdipoR1 and VEGF-A, as well as on vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay. Results: We detected significantly lower levels of AdipoR1 and significantly higher levels of miR-323 in PC specimen. Moreover, the levels of AdipoR1 and miR-323 are inversely correlated. Moreover, miR-323 was found to bind to the 3'UTR of AdipoR1 mRNA to inhibit its translation. Overexpression of miR-323 in PC cells decreased AdipoR1 protein levels, whereas inhibition of miR-323 increased AdipoR1 protein levels, without affecting AdipoR1 transcripts. Moreover, overexpression of miR-323 increased the levels of VEGF-A and the vessel formation by HUVECs, while inhibition of miR-323 decreased the levels of VEGF-A and the vessel formation by HUVECs. Conclusion: Our data demonstrate that miR-323 may increase VEGF-A-mediated cancer vascularization in PC cells through AdipoR1 suppression.

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“…In prostate cancer cells, miR let-7a targets E2F2 and CCND2 to inhibit cell proliferation [ 4 ]. We previously demonstrated that miR let-7a directly targets the 3′ UTR of the IGF1R mRNA and inhibits its expression in prostate cancer cells [ 7 ]. Although accumulating evidences indicate that miR let-7a exerts its anti-tumor activity by regulating oncogenes or tumor suppressor genes [ 8 ], the precise mechanisms of miR let-7a in the pathogenesis of human cancers still remain unclear and the full set of its regulatory substrates need to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

USP35 activated by miR let-7a inhibits cell proliferation and NF-κB activation through stabilization of ABIN-2

et al. 2015

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Ubiquitin specific protease 35 (USP35) is a member of deubiquitylases (DUBs). It remains largely unknown about the biological role and the regulation mechanism of USP35. Here, we first identified miR let-7a as a positive regulator of USP35 expression and showed that USP35 expression positively correlates with miR let-7a expression in different cancer cell lines and tissues. Then, we showed that USP35 expression was decreased dramatically in the tumor tissues compared with the adjacent non-cancerous tissues. USP35 overexpression inhibited cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, we revealed that USP35 acts as a functional DUB and stabilizes TNFAIP3 interacting protein 2 (ABIN-2) by promoting its deubiquitination. Functionally, both ABIN-2 and USP35 could inhibit TNFα-induced NF-κB activation and overexpression of ABIN-2 alleviated USP35-loss induced activation of NF-κB. Collectively, our data indicated that miR let-7a-regulated USP35 can inhibit NF-κB activation by deubiquitination and stabilization of ABIN-2 protein and eventually inhibit cell proliferation. Overall, our study provides a novel rationale of targeting miR let-7a-USP35-ABIN-2 pathway for the therapy of cancer patients.

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The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1 receptor (IGF1R) in prostate cancer PC-3 cells

Cited by 17 publications

References 28 publications

Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

Novel Candidate Key Drivers in the Integrative Network of Genes, MicroRNAs, Methylations, and Copy Number Variations in Squamous Cell Lung Carcinoma

MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor

USP35 activated by miR let-7a inhibits cell proliferation and NF-κB activation through stabilization of ABIN-2

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