MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma

Sun, Xinfang; Sun, Jinping; Hou, Hongtao; Li, Ké; Liu, Xin; Ge, Quan-Xing

doi:10.1007/s13277-016-5444-9

Cited by 20 publications

(15 citation statements)

References 28 publications

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“…Two miRNAs, miR-27b and miR-92a, are overexpressed and can target FBXW7 in HCC. miR-27b inhibits FBXW7 expression and is associated with poor clinical outcome [ 139 ], while miR-92a is inversely correlated with FBXW7 expression, increased cell proliferation, and inhibited apoptosis of HCC [ 140 ]. The lncRNA CASC2 acts as a sponge for miR-367 in HCC samples [ 66 ].…”

Section: Clinical Significance Of Fbxw7 Loss Of Function In Human Canmentioning

confidence: 99%

FBXW7: a critical tumor suppressor of human cancers

2018

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The ubiquitin-proteasome system (UPS) is involved in multiple aspects of cellular processes, such as cell cycle progression, cellular differentiation, and survival (Davis RJ et al., Cancer Cell 26:455-64, 2014; Skaar JR et al., Nat Rev Drug Discov 13:889-903, 2014; Nakayama KI and Nakayama K, Nat Rev Cancer 6:369-81, 2006). F-box and WD repeat domain containing 7 (FBXW7), also known as Sel10, hCDC4 or hAgo, is a member of the F-box protein family, which functions as the substrate recognition component of the SCF E3 ubiquitin ligase. FBXW7 is a critical tumor suppressor and one of the most commonly deregulated ubiquitin-proteasome system proteins in human cancer. FBXW7 controls proteasome-mediated degradation of oncoproteins such as cyclin E, c-Myc, Mcl-1, mTOR, Jun, Notch and AURKA. Consistent with the tumor suppressor role of FBXW7, it is located at chromosome 4q32, a genomic region deleted in more than 30% of all human cancers (Spruck CH et al., Cancer Res 62:4535-9, 2002). Genetic profiles of human cancers based on high-throughput sequencing have revealed that FBXW7 is frequently mutated in human cancers. In addition to genetic mutations, other mechanisms involving microRNA, long non-coding RNA, and specific oncogenic signaling pathways can inactivate FBXW7 functions in cancer cells. In the following sections, we will discuss the regulation of FBXW7, its role in oncogenesis, and the clinical implications and prognostic value of loss of function of FBXW7 in human cancers.

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Section: Clinical Significance Of Fbxw7 Loss Of Function In Human Canmentioning

confidence: 99%

FBXW7: a critical tumor suppressor of human cancers

2018

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“…MiR‐27b regulates cancer development by serving as a tumor suppressor or oncogene . Our study identifies miR‐27b as an inhibitor of USP4.…”

Section: Discussionmentioning

confidence: 80%

Liver X Receptor α–Induced Cannabinoid Receptor 2 Inhibits Ubiquitin‐Specific Peptidase 4 Through miR‐27b, Protecting Hepatocytes From TGF‐β

Kim

et al. 2019

Hepatol Commun

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Liver X receptor‐alpha (LXRα) acts as a double‐edged sword in different biological situations. Given the elusive role of LXRα in hepatocyte viability, this study investigated whether LXRα protects hepatocytes from injurious stimuli and the underlying basis. LXRα activation prevented hepatocyte apoptosis from CCl4 challenges in mice. Consistently, LXRα protected hepatocytes specifically from transforming growth factor‐beta (TGF‐β), whereas LXRα deficiency aggravated TGF‐β‐induced hepatocyte injury. In the Gene Expression Omnibus database analysis for LXR−/− mice, TGF‐β receptors were placed in the core network. Hierarchical clustering and correlation analyses enabled us to find cannabinoid receptor 2 (CB2) as a gene relevant to LXRα. In human fibrotic liver samples, both LXRα and CB2 were lower in patients with septal fibrosis and cirrhosis than those with portal fibrosis. LXRα transcriptionally induced CB2; CB2 then defended hepatocytes from TGF‐β. In a macrophage depletion model, JWH133 (a CB2 agonist) treatment prevented toxicant‐induced liver injury. MicroRNA 27b (miR‐27b) was identified as an inhibitor of ubiquitin‐specific peptidase 4 (USP4), deubiquitylating TGF‐β receptor 1 (TβRI), downstream from CB2. Liver‐specific overexpression of LXRα protected hepatocytes from injurious stimuli and attenuated hepatic inflammation and fibrosis. Conclusion: LXRα exerts a cytoprotective effect against TGF‐β by transcriptionally regulating the CB2 gene in hepatocytes, and CB2 then inhibits USP4‐stabilizing TβRI through miR‐27b. Our data provide targets for the treatment of acute liver injury.

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“…miRNAs are globally deregulated in cancer cells: several oncogenic miRNAs are upregulated, whereas tumor suppressive miRNAs are often suppressed. Thus, therapeutic delivery of tumor suppressive miRNAs and inhibition of oncogenic miRNAs serve as a feasible way to cancer treatment ( 16 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

miR-647 and miR-1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer

Liu

et al. 2017

Molecular Medicine Reports

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MicroRNAs (miRNAs/miRs) have been investigated as diagnostic and prognostic biomarkers for cancer; however, the significance of miRNAs in colorectal cancer (CRC) remains to be elucidated. The aim of the present study was to determine the genetic profiles of CRC tissue, and screen for miRNAs implicated in CRC cell proliferation and migration. RNA sequencing of 10 paired specimens was performed to for screen genes that were upregulated or downregulated in CRC. miRNA expression in CRC specimens and cell lines was confirmed using qPCR analysis. The significance of indicated miRNAs in CRC cell proliferation and migration was evaluated using MTT and scratch wound-healing assays. Online computational prediction, isobaric tags for relative and absolute quantification analysis and a luciferase reporter assay were applied to determine candidate targeted genes for the miRNAs. RNA-seq data revealed miR-1914 as the most prominent miRNA in CRC specimens. qPCR analysis also suggested that the expression of miR-1914, as well as its counterpart miR-647 were elevated in CRC specimens and cell lines. Suppression of miR-647/1914 using small interfering RNAs inhibited CRC SW480 and SW620 cell proliferation, and migration. Nuclear factor I/X (NFIX) was demonstrated to be a candidate for miR-647/1914 and mediated the oncogenic activity of miR-647/1914. In all, miR-647 and miR-1914 were demonstrated to promote the proliferation and migration of CRC cells by directly targeting NFIX. Therapeutic delivery of siRNAs targeting miR-647/1914 and overexpression of NFIX may be feasible approaches for CRC treatment.

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MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma

Cited by 20 publications

References 28 publications

FBXW7: a critical tumor suppressor of human cancers

FBXW7: a critical tumor suppressor of human cancers

Liver X Receptor α–Induced Cannabinoid Receptor 2 Inhibits Ubiquitin‐Specific Peptidase 4 Through miR‐27b, Protecting Hepatocytes From TGF‐β

miR-647 and miR-1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer

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