MiR-199a-5p Loss Up-Regulated DDR1 Aggravated Colorectal Cancer by Activating Epithelial-to-Mesenchymal Transition Related Signaling

Hu, Yingbin; Liu, Jingshi; Jiang, Bingyan; Chen, Juying; Fu, Zhongpin; Bai, Fei; Jiang, Jiarui; Tang, Ziyuan

doi:10.1007/s10620-014-3136-0

Cited by 78 publications

(76 citation statements)

References 32 publications

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“…Specifically, DDR1 and WNT2, previously validated as miR-199a-5p targets (27,42), as well as LIN7C, ARHGAP12, and PALS1 shown in our earlier study were significantly and reversely changed in the bladder SMCs following the alteration of the endogenous miRNA levels by overexpression of miR-199a-5p or antimiR199a-5p. In line with these data, another study demonstrated that overexpression of miR-199a-5p led to decreased DDR1, MMP2, N-cadherin, and vimentin expression (43). In contrast, we did not observe an inhibitory effect of miR-199a-5p on mRNA and protein levels of caveolin 1 (40) either in TEU-2 cells or in the bladder SMCs, which could be attributed to the tissue specificity of the miRNA effects.…”

Section: Journal Of Biological Chemistry 7081supporting

confidence: 87%

MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway

Gheinani

Burkhard

Rehrauer³

et al. 2015

Journal of Biological Chemistry

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Background: MicroRNA miR-199a-5p, implicated in cell motility and proliferation, is highly expressed in bladder smooth muscle. Results: MiR-199a-5p regulates WNT, cytoskeleton, and cell cycle pathways in urothelial and smooth muscle cells and promotes myocardin-driven gene expression. Conclusion: MiR-199a-5p acts via its target WNT2 to control smooth muscle proliferation and morphology. Significance: MiR-199a-5p is a key modulator of smooth muscle hypertrophy, relevant for bladder organ remodeling.

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Section: Journal Of Biological Chemistry 7081supporting

confidence: 87%

MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway

Gheinani

Burkhard

Rehrauer³

et al. 2015

Journal of Biological Chemistry

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“…Accumulating evidence have established an important relationship between EMT and the acquisition of molecular and functional characteristics of cancer stem cells [23, 24]. The reduction of migration and invasion ability may be partly due to the altered EMT-related signaling, such as CDH2 by regulating transcriptional factor SNAI1 [25]. Similar observation was found in breast cancer cells, we discovered that miR-199a-5p greatly suppressed the migration and invasion ability.…”

Section: Discussionsupporting

confidence: 75%

miR-199a-5p confers tumor-suppressive role in triple-negative breast cancer

et al. 2016

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BackgroundTriple-negative breast cancer (TNBC) remains a poor prognostic factor for breast cancer since no effective targeted therapy is readily available. Our previous studies confirmed miR-199a-5p is a TNBC-specific circulating biomarker, however, its functional roles in breast cancer is largely unknown. Thus, we investigated the functional implication of miR-199a-5p in TNBC and its potential underlying mechanisms.MethodsMTT assay was performed to investigate the cell proliferation after transient transfection of miR-199a-5p in MDA-MB-231 cell line, followed by cell cycle analysis. Transwell invasion assay and wound healing assay were used to study the invasion and migration ability respectively. To further investigate the stemness-related characteristics of miR-199a-5p in breast cancer cells, single-cell clonogenic assay and aldehyde dehydrogenase (ALDH) assay were performed. 32 normal and 100 breast cancer patients’ plasma were recruited to identify the potential circulating markers by qPCR.ResultsCell proliferation assay revealed significant inhibition after miR-199a-5p ectopic expression (p < 0.0001), as a result of decreased S phase (p = 0.0284), increased G0/G1 phase (p = 0.0260) and apoptosis (p = 0.0374). Invasiveness (p = 0.0005) and wound healing ability were also decreased upon miR-199a-5p overexpression. It significantly altered EMT-related genes expression, namely CDH1, ZEB1 and TWIST. Single-cell clonogenic assay showed decreased colonies in miR-199a-5p (p = 0.0182). Significant downregulation (p = 0.0088) and inhibited activity (p = 0.0390) of ALDH was observed in miR-199a-5p. ALDH1A3, which is the dominant isoform of ALDH, is significantly upregulated in breast cancer plasma especially in TNBC (p = 0.0248). PIK3CD was identified as a potential downstream target of miR-199a-5p.ConclusionsTaken together, we unraveled, for the first time, the tumor-suppressive role of miR-199a-5p in TNBC, which attributed to EMT and cancer stemness properties, providing a novel therapeutic options towards this aggressive disease.

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“…For instance, miR-199a-5p was observed to be downregulated in triple-negative breast cancer, and its levels in plasma were notably restored upon surgical resection, suggesting that it may be involved in the development of breast cancer (17). Hu et al reported that miR-199a-5p was frequently downregulated in colorectal cancer, which led to the upregulation of discoidin domain receptor 1 and the activation of epithelialto-mesenchymal transition-related signaling (16). In addition, the expression level of miR-199a-5p was significantly increased in gastric cancer tissues compared with paired normal tissues, and higher miR-199a-5p level was associated with increased lymph node metastasis and higher tumor-node-metastasis stage, suggesting that miR-199a-5p may act as an oncogene in gastric cancer (26).…”

Section: Mir-199a-5p Negatively Mediates the Protein Expression Of Bementioning

confidence: 99%

“…Through negatively mediation of their targets, miRs have been implicated in numerous cellular processes, including cell survival, proliferation, differentiation, apoptosis and autophagy (13). miR-199a-5p has been observed to be deregulated and important in a variety of human cancers, including gastric cancer, non-small cell lung cancer, melanoma and colorectal cancer (14)(15)(16)(17)(18). In addition, miR-199a-5p also has an inhibitory effect on autophagy (19,20).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

Jiang

et al. 2016

Oncology Letters

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Abstract. Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells. In addition, DDP treatment also upregulated the protein levels of light chain 3 (LC3)-II and Beclin1 as well as the ratio of LC3-II vs. LC3-I in MG63 cells, indicating that autophagy was activated. Restoration of miR-199a-5p expression promoted DDP-induced inhibition of MG63 cell proliferation and inhibited DDP-induced autophagy, as indicated by the reduced protein levels of LC3-II and Beclin1 and the ratio of LC3-II vs. LC3-I. Finally, luciferase reporter assay data revealed that miR-199a-5p directly targeted Beclin1 and negatively mediated Beclin1 expression at a post-transcriptional level in MG63 cells. In conclusion, our study suggests that miR-199a-5p promotes the cytotoxicity of DDP in OS cells via inhibition of autophagy. Therefore, miR-199a-5p/autophagy signaling is involved in chemoresistance and may become a potential target for the treatment of DDP-resistant OS.

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MiR-199a-5p Loss Up-Regulated DDR1 Aggravated Colorectal Cancer by Activating Epithelial-to-Mesenchymal Transition Related Signaling

Abstract: Our findings indicated that up-regulation of DDR1 induced by miR-199a-5p down-regulation may contribute to the development and progression of CRC, and this effect may be associated with increased invasiveness, at least in part, via activating the EMT-related signaling.

Cited by 78 publications

References 32 publications

MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway

MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway

miR-199a-5p confers tumor-suppressive role in triple-negative breast cancer

MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

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