VHL-Regulated MiR-204 Suppresses Tumor Growth through Inhibition of LC3B-Mediated Autophagy in Renal Clear Cell Carcinoma

Mikhaylova, Olga; Stratton, Yiwen; Hall, Daniel; Kellner, Emily; Ehmer, Birgit; Drew, Angela F.; Gallo, Catherine A.; Plas, David R.; Biesiada, Jacek; Meller, Jarosław; Czyzyk-Krzeska, Maria F.

doi:10.1016/j.ccr.2012.02.019

Cited by 284 publications

(266 citation statements)

References 44 publications

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“…Thus, the role and mechanism of miR-7 in SBNETs merits further investigation, and it would also be important to evaluate ciRS-7 expression. Similarly, whilst we found upregulation of miR-204 in SBNETs, it has been seen as downregulated in gastric cancer (Sacconi et al 2012, colorectal cancer (Yin et al 2014) and clear cell renal cell carcinoma (Mikhaylova et al 2012). Thus, its increased expression and role in SBNETs remains unknown.…”

Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 43%

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.

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Section: Global Mirna Profiling Reveals a Signature Specific For Smalmentioning

confidence: 43%

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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“…miRNAs are known to contribute to multiple tumorigenic steps in human cancers, including RCC. Recent studies have identified regulatory activities of miRNAs in ccRCC cell growth (4)(5)(6)(7)(8), apoptosis (5,6,8,9), migration, and invasion (5)(6)(7)(8). A predominant and systemic alteration in miRNA expression during renal carcinogenesis has been indicated by present studies of miRNA expression profiling (10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 71%

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

Chen

Wang

Ruan

et al. 2014

Clinical Cancer Research

124

117

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Purpose: Although microRNAs (miRNA) have been revealed as crucial modulators of tumorigenesis, our understanding of their roles in renal cell carcinoma (RCC) is limited. Here we sought to identify human miRNAs that act as key regulators of renal carcinogenesis.Experimental Design: We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues.Results: A total of 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an area under the receiver operating characteristics curve of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G 0 -G 1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the antitumor activities of miR-141 were mediated by its reversal regulation of erythropoietin-producing hepatocellular (Eph) A2 (EphA2), which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9.

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“…In addition, downregulation of miR-204 has been documented in several types of cancers. [37][38][39][40][41] Decreased expression of miR-204 results in overexpression of its target, myeloid cell leukemia sequence 1 (Mcl-1) mRNA, and induces anti-apoptotic signaling in pancreatic cancers. 42 miR-204 also regulates expression of an oncogene, neurotrophic receptor tyrosine kinase B, and promotes metastasis in endometrial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3′ UTR of BCL2 mRNA

et al. 2014

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VHL-Regulated MiR-204 Suppresses Tumor Growth through Inhibition of LC3B-Mediated Autophagy in Renal Clear Cell Carcinoma

Cited by 284 publications

References 44 publications

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression

Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3′ UTR of BCL2 mRNA

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