MicroRNA Profile of Tumorigenic Cells During Carcinogenesis of Lung Adenocarcinoma

Zhao, Zhenguo; Jin, Jun-yu; Zhang, An-mei; Zhang, Luping; Wang, Xinxin; Sun, Jianping; Chen, Zhengtang

doi:10.1002/jcb.24999

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…It is likely that such changes in the protease web may also contribute to the different vascularization of tumors in Mmp8 -wild-type, −heterozygote and -null mice. With the recent link that has been forged between MMP-8 and miR-21 [ 15 ], and recognition of the impact of microRNAs on the expression of several key degradome players, for example MMP-3, MMP-13 and TIMP-2, the effects of MMP-8 ablation on miRNA expression might be an interesting avenue for future research [ 53 - 61 ].…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

et al. 2015

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IntroductionMatrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types.MethodsWe have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to explore the effects of loss of MMP-8 on the incidence and progression of mammary carcinomas.ResultsIn this aggressive mouse model of breast cancer, loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT; Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the 14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a lower vascularity than their heterozygote and null counterparts. No differences in macrophage infiltration were apparent throughout primary tumor development, though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild-type tumors. Using quantitative real-time RT-PCR, we tracked the expression of the entire Mmp and Timp gene families, observing a significant decrease in Mmp3 expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout the time course of the model, which was confirmed at the protein level.ConclusionsThese findings provide novel insight into the suppressive action of MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP-8 likely has pleiotropic effects on innate immunity and angiogenesis that are reflected in changes in the protease web.

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Section: Discussionmentioning

confidence: 99%

Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

et al. 2015

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“…They can negatively regulate gene expression at the post-transcriptional level predominantly by WatsonCrick base pairing to the 3'-UTR of target messenger RNA (Lambert et al, 2011). They represent only a small proportion of the genome, but can regulate almost onethird of human genes, and are involved in most biological and pathological processes, such as organ growth and development (Aparicio et al, 2014), cell proliferation and differentiation as well as tumorigenesis and cancer progression (Ni et al, 2014;Rupaimoole et al, 2014;Zhao et al, 2014). Polymorphisms in the miRNA are emerging as powerful tools to study the biology of a disease and have the potential to be used as diagnostic and prognostic biomarkers in diseases (Joshi et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Rs895819 within miR-27a Might be Involved in Development of Non Small Cell Lung Cancer in the Chinese Han Population

Yan²,

Yang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings.

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“…These findings imply that the dysregulation of miRNAs may contribute to several malignant processes including cancer cell cycle, apoptosis, invasion, migration and metastasis by affecting the corresponding transcripts (13). miR-615-5p, located in CpG islands of the HoX gene cluster on chromosome 12q13.13, has been determined to be frequently downregulated and functions as a tumor suppressor in various human cancers via specially binding to the complimentary recognition sequences in the 3'-untranslated region (3'uTR) of the corresponding target mRNAs (14)(15)(16). However, little is known regarding its involvement in human ESCC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-615-5p targets insulin-like growth factor 2 and exerts tumor-suppressing functions in human esophageal squamous cell carcinoma

Yang

Xie

et al. 2017

Oncol Rep

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To investigate the expression pattern, clinical significance and functional roles of microRNA (miR)-615-5p in human esophageal squamous cell carcinoma (ESCC), , quantitative real-time PCR was performed to detect expression levels of miR‑615‑5p in ESCC tissues and cell lines. Associations between miR‑615‑5p expression and various clinicopathological features of ESCC patients were also statistically evaluated. The candidate targets of miR‑615‑5p were identified by integrating bioinformatics miRNA target prediction, western blot analysis and luciferase reporter assay. Moreover, the functions of miR‑615‑5p in ESCC cell migration and invasion were determined using the transfection of miRNA mimics, or co-transfected with miRNA mimics and the expression vector of its target gene. As a result, miR‑615‑5p expression in ESCC tissues and cells were markedly lower than those in non-cancerous esophageal mucosa and human normal esophageal cells, respectively (both P<0.001). miR‑615‑5p downregulation was significantly associated with advanced tumor-node-metastasis stage, positive lymph node metastasis and moderate-poor differentiation. Functionally, the re-expression of miR‑615‑5p suppressed the invasion and migration of ESCC cells in vitro. Interestingly, insulin-like growth factor 2 (IGF2) was identified as a direct target gene of miR‑615‑5p, and the inhibitory effects of miR‑615‑5p in ESCC cell motility were reversed by the restoration of IGF2 expression. In conclusion, miR‑615‑5p downregulation may be an underlying molecular mechanism of development and progression of ESCC, and may function as a potential therapeutic target of this malignancy. Also, we illustrate that the miR‑615‑5p/IGF2 axis may bring important contributions to cell motility of human ESCC.

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MicroRNA Profile of Tumorigenic Cells During Carcinogenesis of Lung Adenocarcinoma

Cited by 16 publications

References 37 publications

Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Rs895819 within miR-27a Might be Involved in Development of Non Small Cell Lung Cancer in the Chinese Han Population

MicroRNA-615-5p targets insulin-like growth factor 2 and exerts tumor-suppressing functions in human esophageal squamous cell carcinoma

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