miR-143 Inhibits NSCLC Cell Growth and Metastasis by Targeting Limk1

Xia, Hui; Sun, Shengjie; Wang, Bo; Wang, Tao; Liang, Chaoyang; Guo, Li; Huang, Chongbiao; Qi, Daliang; Chu, Xiangyang

doi:10.3390/ijms150711973

Cited by 48 publications

(31 citation statements)

References 30 publications

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“…5A). These data suggest that LIMK1 is a likely target of miR-143 in these As-CSC cells, consistent with reports of miR-143 directly targeting LIMK1in non-small cell lung cancer (NSCLC) (Xia et al 2014). To ensure that the decrease in LIMK1 protein levels is not caused by other upstream regulators of LIMK1 such as Rac, ROCK and PAK1 (Manetti 2012), we examined the protein levels of these regulators.…”

Section: Resultssupporting

confidence: 90%

“…These data are consistent with other reports showing that miR-143 restoration decreased the proliferation of the prostate cancer cell lines DU145, PC3, LNCaP and C4-2 enhancing their sensitivity to docetaxel (Xu et al 2011), and abrogating tumor growth in mice (Clape et al 2009). Similarly, miR-143 is downregulated in various cancer cells including leukemia cells (Shen et al 2014), non-small cell lung cancer (NSCLC) (Xia et al 2014), cervical cancer (Lipeng et al 2012), and melanoma cells (Li et al 2014). Restoration of miR-143 in these cancer cells inhibited cell proliferation and induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Ngalame

Makia

Waalkes

et al. 2016

Toxicology and Applied Pharmacology

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Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Ngalame

Makia

Waalkes

et al. 2016

Toxicology and Applied Pharmacology

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“…MicroRNAs play critical roles in tumorigenesis, tumor cell proliferation, migration, invasion, metastasis and angiogenesis (Iuliano et al 2013;Di Leva et al 2014). A large number of microRNAs have been aberrantly found in NSCLC, and many of them contribute to NSCLC development and progression (Chen et al 2013b;Xia et al 2014b;Xia et al 2014a). The role of microRNAs may be altered between NSCLC (Hu et al 2008) and SCLC (Liu and Chen 2011), thus we only focus on NSCLC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-141 Is a Biomarker for Progression of Squamous Cell Carcinoma and Adenocarcinoma of the Lung: Clinical Analysis of 125 Patients

Zhang

Rong

et al. 2015

Tohoku J. Exp. Med.

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Lung cancer is the most common malignant tumor worldwide. MicroRNA has become an ideal biomarker for cancer diagnosis, prognosis and therapy. The relationship between microRNA-141 and non-small cell lung cancer (NSCLC) is contradictory. Thus, in current study, we aimed to investigate the level of microRNA-141 in NSCLC tissues and to evaluate its potential clinical value. This study enrolled 125 NSCLC patients (75 males and 50 females) with a median age of 61 years (range, 23-90 years). NSCLC patients included 23 squamous cell carcinomas (SCCs), 101 adenocarcinomas (ADCs) and 1 large cell carcinoma. The expression level of microRNA-141 was significantly higher in NSCLC tissues than in adjacent lung tissues (P < 0.001), detected by real time RT-PCR. Receiver operating characteristic (ROC) exhibited a moderate diagnostic value of microRNA-141 for NSCLC with the area under curve of 0.707. The microRNA-141 expression increased with the larger tumor size (P = 0.002), lymph node metastasis (P = 0.018) and advanced stage (P = 0.022) in NSCLC patients. For subgroup analysis, microRNA-141 expression in SCC was correlated with tumor size (r = 0.490, P = 0.018), and in ADC, microRNA-141 level was positively associated with tumor size (r = 0.222, P = 0.026), lymph node metastasis (r = 0.242, P = 0.015) and TNM stage (r = 0.210, P = 0.035). Furthermore, univariate analysis revealed that the expression of microRNA-141 was an independent prognostic indicator of ADC. In conclusion, microRNA-141 is a potential biomarker for the molecular diagnosis and risk stratification of NSCLC.

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“…The expression of mRNAs in the MIR143HG-associated PPI module in secretory LUSC were all positively correlated with MIR143HG, and these mRNAs were enriched in functions related to extracellular matrix organization and cell adhesion (Figure S10). Many studies have reported that the overexpression of miR-143 inhibited cell migration and invasion3738. Hence, MIR143HG and miR-143 might be involved in similar biological processes via different regulatory mechanisms, whereby MIR143HG activates targets and miR-143 represses targets.…”

Section: Resultsmentioning

confidence: 99%

Identification of lncRNA functions in lung cancer based on associated protein-protein interaction modules

Wu¹,

Hsu

Lu³

et al. 2016

Sci Rep

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Long non-coding RNAs (lncRNAs) have been found to play important roles in various biological processes; however, many of their functions remain unclear. In this study, we present a novel approach to identify the lncRNA-associated protein-protein interaction (PPI) modules and ascertain their functions in human lung squamous cell carcinoma. We collected lncRNA and mRNA expression profiles of lung squamous cell carcinoma from The Cancer Genome Atlas. To identify the lncRNA-associated PPI modules, lncRNA-mRNA co-expression networks were first constructed based on the mutual ranks of expression correlations. Next, we examined whether the co-expressed mRNAs of a specific lncRNA were closely connected by PPIs. For this, a significantly connected mRNA set was considered to be the lncRNA-associated PPI module. Finally, the prospective functions of a lncRNA was inferred using Gene Ontology enrichment analysis on the associated module. We found that lncRNA-associated PPI modules were subtype-dependent and each subtype had unique molecular mechanisms. In addition, antisense lncRNAs and sense genes tended to be functionally associated. Our results might provide new directions for understanding lncRNA regulations in lung cancer. The analysis pipeline was implemented in a web tool, available at http://lncin.ym.edu.tw/.

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miR-143 Inhibits NSCLC Cell Growth and Metastasis by Targeting Limk1

Cited by 48 publications

References 30 publications

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

MicroRNA-141 Is a Biomarker for Progression of Squamous Cell Carcinoma and Adenocarcinoma of the Lung: Clinical Analysis of 125 Patients

Identification of lncRNA functions in lung cancer based on associated protein-protein interaction modules

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