MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells

Jx, Cao; Lu, Ye; Jj, Qi; Gs, An; Zb, Mao; Ht, Jia; Sy, Li; Jh, Ni

doi:10.1038/cddis.2014.386

Cited by 43 publications

(46 citation statements)

References 55 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports have shown that miR-630 decreases apoptotic cell death by blocking PTEN expression but inhibits proliferation in breast and lung cancers [9–11]. In our study, miR-630 had no effect on proliferation.…”

Section: Discussioncontrasting

confidence: 62%

MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) is the key process that drives tumor metastasis. Accumulating evidence suggests that the deregulation of some microRNAs (miRNAs), is implicated in this process. Here, we highlight the function and molecular mechanism of miR-630 and its potential clinical application in hepatocellular carcinoma (HCC). First, we identified the clinical relevance of miR-630 expression in a screen of 97 HCC patient tissues. Patients with low miR-630 expression had higher recurrence rates and shorter overall survival than those with high miR-630 expression. Functional studies demonstrated the overexpression of miR-630 in HCC cells attenuated the EMT phenotype in vitro. Conversely, inhibition of miR-630 promoted EMT in HCC cells. Mechanistically, our data revealed that miR-630 suppressed EMT by targeting Slug. Knockdown of Slug expression reversed miR-630 inhibitor-mediated EMT progression. Furthermore, we found that the TGF-β-Erk/SP1 and JNK/c-Jun signaling pathways repressed miR-630 transcription through occupying transcription factor binding sites. Ectopic expression of miR-630 restored the TGF-β-activated EMT process. Taken together, these findings demonstrate, in HCC cells, miR-630 exerts its tumor-suppressor functions through the TGF-β-miR-630-Slug axis and provides a potential prognostic predictor for HCC patients.

show abstract

Section: Discussioncontrasting

confidence: 62%

MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These authors also showed that miR-630 was upregulated in a majority of ccRCC patients and that miR-630 expression was an independent prognostic factor for patients with renal cancer . Moreover, Cao et al (2014b) demonstrated that miR-630 targets CDC7, thereby inhibiting CDC7-mediated initiation of DNA synthesis and inducing G1 arrest. However, miR-630 has a bimodal role in the regulation of apoptosis because of its multiple target effects, which maintains apoptotic balance under genotoxic stress.…”

Section: Discussionmentioning

confidence: 99%

“…PTEN, which is wellknown for its role in tumor growth, invasion, and metastasis, has been reported as a tumor suppressor gene in ovarian cancer (Kurose et al, 2001;Lee and Park, 2009) with implications in ovarian cancer cell resistance to cisplatin (Wu et al, 2008b;Singh et al, 2013). MiR-630 gets involved in tumorigenesis by targeting different molecules such as BCL2, BCL2L2, CDC7, and IGF-1R (Galluzzi et al, 2010;Huang et al, 2011;Cao et al, 2014b). As an miRNA may possess multiple targets, we speculated that miR-630-induced cell proliferation and migration and that apoptosis may be linked to PTEN.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-630 inhibits cell proliferation and invasion and enhances chemosensitivity in human ovarian carcinoma

Zou¹,

Gao²,

Wang³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-23 nt long) that can target genes for either degradation of mRNA or inhibition of translation. miRNAs have not been comprehensively studied in human epithelial ovarian carcinoma (EOC). MicroRNA-630 (miR-630) has been frequently observed to be aberrantly expressed in various types of tumors. The present study explored the functions of miR-630 in the proliferation, apoptosis, chemosensitivity, and invasion of EOC. Using real-time polymerase chain reaction, we detected the miR-630 expression in cancerous, benign, and normal human ovarian tissues. Then, we evaluated the role of miR-630 in cell proliferation, chemosensitivity, apoptosis, and invasion by using the Cell Counting Kit-8, Annexin-V/FITC, and transwell assay on A2780 and SKOV3 cells. Western blotting was performed for analyzing the phosphatase and tensin homolog gene (PTEN) protein expression. The miR-630 expression level was higher in ovarian cancerous tissues than in benign and normal ovarian tissues. Decreased expression of miR-630 suppressed EOC cells' proliferation, migration, and invasion as well as significantly enhanced cell apoptosis and chemosensitivity to cisplatin. Furthermore, PTEN expression was increased in A2780 cells transfected by miR-630 inhibitor in comparison with inhibitor-negative control-transfected cells. In conclusion, downregulation of miR-630 dramatically increased apoptotic cell death chemosensitivity to cisplatin and decreased the proliferation, invasion, and migration of EOC cells. MiR-630 may thus play an important role in the biological behaviors of EOC cells through negative control of the PTEN expression.

show abstract

“…MiR-630 inhibits cell proliferation by targeting cell-cycle kinase 7 (CDC7), but maintains the apoptotic balance by targeting multiple activators of apoptosis under genotoxic stress. On the one hand, miR-630 promotes apoptosis via blocking CDC7-mediated initiation of DNA synthesis; on the other hand, it reduces apoptosis by targeting several other apoptotic modulators such as PARP3, DDIT4, EP300 and EP300 downstream effector p53, thereby maintaining the apoptotic balance [26].…”

Section: Cddp Regulates Mirna Processingmentioning

confidence: 99%

MicroRNAs as Regulators of Cisplatin Resistance in Lung Cancer

Chen

Gao

Zhang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Cisplatin (CDDP) is one of the most effective broad-spectrum anticancer drugs, which has been employed for the treatment of lung cancer. The development of CDDP resistance is a major problem of tumor chemotherapy. MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs, involved in the initiation and progression of human cancer. Increasing evidence has shown that dysregulation of miRNAs is involved in chemo resistance of tumor cells to anti-cancer drugs, including CDDP. This article summarizes current research involving miRNAs as regulators of key target genes for CDDP resistance in lung cancer. Potential use of targeting miRNAs can lead to miRNA-based therapies, which will be helpful for overcoming drug resistance and developing more effective personalized anti-cancer treatment strategies in human lung cancers.

show abstract

MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells

Cited by 43 publications

References 55 publications

MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma

MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma

Downregulation of microRNA-630 inhibits cell proliferation and invasion and enhances chemosensitivity in human ovarian carcinoma

MicroRNAs as Regulators of Cisplatin Resistance in Lung Cancer

Contact Info

Product

Resources

About