MicroRNA181c inhibits prostate cancer cell growth and invasion by targeting multiple ERK signaling pathway components

Su, Zhengzheng; Zhang, Mengni; Xu, Miao; Li, Xinglan; Tan, Jun; Xu, Yinghao; Pan, Xiuyi; Chen, Ni; Chen, Xueqin; Zhou, Qiao

doi:10.1002/pros.23478

Cited by 12 publications

(5 citation statements)

References 54 publications

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“…(33)(34)(35) Multiple molecules act as targets for miR-181c, including Six2 in metanephric mesenchymal cells, FoxO1 in diabetic endothelial cells, transforming growth factor β in glioblastoma cells, PRKCD in ovarian cells, and Erk in prostate cancer cells. (35)(36)(37)(38)(39) Here, we focused on the functional importance of miR-181c down-regulation in HCV-infected hepatocytes. We have observed that HCV-associated down-regulation of miR-181c targets the 3′-UTR, leading to enhanced ATM expression.…”

Section: Discussionmentioning

confidence: 99%

“…Suppression of miR‐181c may be a prognostic indicator in rapidly proliferating cells, like glioblastoma, osteosarcoma, and ovarian carcinoma . Multiple molecules act as targets for miR‐181c, including Six2 in metanephric mesenchymal cells, FoxO1 in diabetic endothelial cells, transforming growth factor β in glioblastoma cells, PRKCD in ovarian cells, and Erk in prostate cancer cells . Here, we focused on the functional importance of miR‐181c down‐regulation in HCV‐infected hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis C Virus Mediated Inhibition of miR‐181c Activates ATM Signaling and Promotes Hepatocyte Growth

Patra¹,

Meyer²,

Ray³

et al. 2019

Hepatology

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Background and Aims Hepatitis C virus (HCV) infection promotes hepatocyte growth and progress to hepatocellular carcinoma. We previously observed that HCV infection of hepatocytes transcriptionally down‐regulates miR‐181c expression through CCAAT/enhancer binding protein β (C/EBP‐β). Here, we examined the role of miR‐181c in the regulation of cell cycle progression in relation to HCV infection. In silico analysis suggested that ataxia‐telangiectasia mutated (ATM) protein, a protein kinase, is a direct target of miR‐181c. ATM is a central mediator of response for cellular DNA double‐strand break. Approach and Results Our results demonstrated that ATM expression is higher in HCV‐infected hepatocytes and chronic HCV‐infected liver biopsy specimens. We have shown a direct interaction of miR‐181c with the 3′ untranslated region of ATM, and the presence of ATM in miR‐181c‐associated RNA‐induced silencing complex. Exogenous expression of miR‐181c inhibited ATM expression and activation of its downstream molecules, Chk2 and Akt. On the other hand, introduction of anti‐miR‐181c restored ATM and phosphorylated Akt. Furthermore, introduction of miR‐181c significantly inhibited phospho–cyclin‐dependent kinase 2 (CDK2) and cyclin‐A expression, arresting cell cycle progression, whereas overexpression of miR‐181c promoted apoptosis of HCV‐infected hepatocytes and can be inhibited by overexpression of ATM from a clone lacking miR‐181c binding sites. In addition, miR‐181c significantly regressed tumor growth in the xenograft human hepatocellular carcinoma mouse model. Conclusions Together, our results suggest that HCV infection suppresses miR‐181c in hepatocytes, resulting in ATM activation and apoptosis inhibition for promotion of cell cycle progression. The results provide mechanistic insight into understanding the role of miR‐181c in HCV‐associated hepatocyte growth promotion, and may have the potential for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Mediated Inhibition of miR‐181c Activates ATM Signaling and Promotes Hepatocyte Growth

Patra¹,

Meyer²,

Ray³

et al. 2019

Hepatology

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“…In addition, it is closely related to tumor formation. Increased expression of ERK has been detected in a variety of human tumors, − especially in GC. It has been shown that the activation of ERK signaling promotes GC growth and metastasis, so it is the most important pathway in the development of GC .…”

Section: Resultsmentioning

confidence: 99%

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

et al. 2022

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Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0−G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

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“…Jung et al13 reported that NFE2L2/NRF2 activity was linked to mitochondria and AMP-activated protein kinase signaling in cancers via miR-181c/mitochondria-encoded cytochrome c oxidase regulation. Su et al14 reported that miR-181c inhibited the growth and invasion of prostate cancer cells by targeting multiple ERK signaling pathway components. Yao et al15 reported that miR-181c inhibited ovarian cancer metastasis and progression by targeting PRKCD expression.…”

Section: Discussionmentioning

confidence: 99%

<p>MicroRNA-181c suppresses growth and metastasis of hepatocellular carcinoma by modulating NCAPG</p>

Gong

et al. 2019

CMAR

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Purpose: Numerous studies have shown that the expression of microRNA-181c (miR-181c) is inhibited in various cancers, which suggests that it has a cancer suppressive effect. In the current study, we evaluated the regulation and characteristics of miR-181c in human hepatocellular carcinoma (HCC). Materials and methods: Samples of tumor tissues and adjacent non-tumor tissues were collected from 52 patients with HCC, and expression levels of miR-181c in these samples were investigated via quantitative real-time polymerase chain reaction. HCC cell migration and invasion were investigated via wound healing assays and transwell assays. HCC cell apoptosis rates were assessed via flow cytometry, and HCC proliferation was assessed via 5-ethynyl-20-deoxyuridine assays. In vivo tumors were initiated by subcutaneously inoculating HCC cells into nude mice. And various biomarkers were investigated via western blotting. Results: In microarray datasets and tumor tissues, significant downregulation of miR-181c was apparent compared with non-tumorous adjacent tissues. Expression of miR-181c in HCC cells was also significantly lower than it was in normal human liver cells. miR-181c regulated the migration, invasion, apoptosis, and proliferation of HCC cell lines in vitro, and tumor development in vivo. Observations also suggest that miR-181c regulates NCAPG in HCC cells, and its expression affects cellular invasion, migration, proliferation, and apoptosis. There was a negative correlation between miR-181c expression and NCAPG in HCC tissue samples. Conclusion: miR-181c exhibits tumor-suppression via the regulation of NCAPG levels.

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MicroRNA181c inhibits prostate cancer cell growth and invasion by targeting multiple ERK signaling pathway components

Abstract: Downregulation of miR181c results in deregulated ERK signaling and promotes prostate cancer cell growth and metastasis.

Cited by 12 publications

References 54 publications

Hepatitis C Virus Mediated Inhibition of miR‐181c Activates ATM Signaling and Promotes Hepatocyte Growth

Hepatitis C Virus Mediated Inhibition of miR‐181c Activates ATM Signaling and Promotes Hepatocyte Growth

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission

<p>MicroRNA-181c suppresses growth and metastasis of hepatocellular carcinoma by modulating NCAPG</p>

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