MiR-224 Targets the 3′UTR of Type 1 5′-Iodothyronine Deiodinase Possibly Contributing to Tissue Hypothyroidism in Renal Cancer

Bogusławska, Joanna; Wójcicka, Anna; Piekiełko-Witkowska, Agnieszka; Master, Adam; Nauman, A

doi:10.1371/journal.pone.0024541

Cited by 72 publications

(53 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Changes in the intracellular TH concentration due to alterations in the deiodinases status seem to be critical for modulating cell proliferation and differentiation. Studies in clear cell renal cell carcinoma (ccRCC) have shown that the loss of DIO1 expression, mediated by miR-224 induction, resulted in diminishing intratumoral T 3 concentration which contributes to the intracellular hypothyroidism observed in ccRCC (Boguslawska et al 2011). Additionally, experimental studies in BCC and in colon tumor cells have shown that the increase in the DIO3 levels accompanied of DIO2 reduction would be associated with the induction of cell proliferation, by overexpression of cyclin D1.…”

Section: Discussionmentioning

confidence: 99%

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metast atic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF V600E ) and, at lower levels, in TPC-1 (RET/PTC1) cells (P!0.007 and PZ0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF V600E mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P!0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 mM), MEK (U0126, 10-20 mM) or p38 (SB203580, 10-20 mM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 mM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA-mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness.

show abstract

Section: Discussionmentioning

confidence: 99%

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Recent evidence has shown that miRNAs play essential roles in multiple biological processes related to cancer, including cell differentiation, proliferation, tumorignesis, angiogenesis, invasion, and metastasis (18)(19)(20). Upregulation of miR-224 has only been observed in a few tumor types, such as hepatocellular carcinoma, pancreatic ductal carcinoma, breast and renal cancer (21)(22)(23)(24). Importantly, in hepatocellular carcinoma, p65/NF-kB has been shown to act as a direct transcriptional regulator of miR-224 expression, which links upregulation of miR-224 with cell migration and invasion (21).…”

Section: Discussionmentioning

confidence: 99%

microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

Liao

Wang

et al. 2013

Clinical Cancer Research

110

View full text Add to dashboard Cite

Purpose: To investigate the clinicopathologic significance, role, and mechanism of action of microRNA-224 (miR-224) in colorectal cancer.Experimental Design: Real-time PCR was used to quantify miR-224 expression. The association of miR-224 with the clinicopathologic features and survival was evaluated in 110 colorectal cancer patients. The role of miR-224 in colorectal cancer was investigated using in vitro and in vivo assays. Luciferase reporter assays were conducted to confirm target gene associations.Results: miR-224 was overexpressed in colorectal cancer. High-level expression of miR-224 was significantly associated with an aggressive phenotype and poor prognosis. Overexpression of miR-224 promoted colorectal cancer cell proliferation in vitro and tumor growth in vivo. Specifically, miR-224 accelerated the G 1 -S phase transition through activation of AKT/FOXO3a signaling, downregulation of p21Cip1 and p27Kip1, and upregulation of cyclin D1. Moreover, both PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, antagonists of PI3K/AKT signaling, were confirmed as bona fide targets of miR-224. miR-224 directly targeted the 3 0 -untranslated regions of the PHLPP1 and PHLPP2 mRNAs and repressed their expression. Conclusion: This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer. miR-224 not only plays important roles in the regulation of cell proliferation and tumor growth in colorectal cancer, but also has potential as a prognostic marker or therapeutic target for colorectal cancer.

show abstract

“…miR-224 is reported to be overexpressed in various types of cancer (15)(16)(17)(18)(19)(20), and it plays critical roles in malignant phenotypes. Consistent with these previous observations, miR-224 was found to be upregulated in HepG2 cells in our study.…”

Section: Discussionmentioning

confidence: 99%

“…The abnormal expression of miR-224 has been reported in several human cancers (15)(16)(17)(18)(19). Wang et al found that miR-224 is upregulated in HCC patients and HCC cell lines (20), and promotes HCC cell apoptosis by targeting the transcript expression levels of apoptosis inhibitor 5 (API-5).…”

Section: Introductionmentioning

confidence: 99%

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Ma¹,

Tao²,

Gao³

et al. 2012

Oncology Letters

View full text Add to dashboard Cite

Abstract. microRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate gene expression. Increasing evidence has shown that the deregulation of miRNAs is linked to cancer. The overexpression of miR-224 has been reported in several human cancers. The aim of the present study was to investigate the function of miR-224 in the pathogenetic process of hepatocellular carcinoma (HCC), and the precise mechanism underlying its function. Both gain-of-function and loss-of function assays were conducted through transfection with miR-224 mimics and miR-224 inhibitors in the HepG2 liver carcinoma cell line. The data revealed that miR-224 exerts a significant role in promoting cell proliferation, migration and invasion. Western blot analysis showed that the phosphorylation levels of AKT positively correlated with endogenous levels of miR-224. In addition, results from a dual luciferase reporter assay showed that the expression of the serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A β isoform (PPP2R1B) is inhibited by miR-224; thus, it appears that PPP2R1B is a candidate target of miR-224 in HCC. These data suggest that miR-224 plays a significant role in HCC, possibly through the activation of the AKT signaling pathway by targeting PPP2R1B.

show abstract

MiR-224 Targets the 3′UTR of Type 1 5′-Iodothyronine Deiodinase Possibly Contributing to Tissue Hypothyroidism in Renal Cancer

Cited by 72 publications

References 60 publications

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

microRNA-224 Promotes Cell Proliferation and Tumor Growth in Human Colorectal Cancer by Repressing PHLPP1 and PHLPP2

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Contact Info

Product

Resources

About