MicroRNA Expression Profiles in Korean Non-Small Cell Lung Cancer

Son, Ji Woong; Kim, Young Jin; Cho, Hyun Min; Lee, Soo Young; Jang, Jin Sung; Choi, Jin Eun; Lee, Jung Uee; Kang, Min Gyu; Lee, Yu Mi; Kwon, Sun Jung; Choi, Eugene; Na, Moon Jun; Park, Jae Yong

doi:10.4046/trd.2009.67.5.413

Cited by 16 publications

(21 citation statements)

References 37 publications

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“…A series of minimalistic studies with less than ten patients (SO, G10, YG, G11, MA and LE) analysed samples of mostly Asian origin 19, 20, 22, 25, 26. The results of one of them, LE, are least related to other datasets and do not match any of the meta‐signature miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Meta‐analysis of microRNA expression in lung cancer

Võsa

Vooder

Kolde

et al. 2012

Intl Journal of Cancer

190

127

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The prognostic and diagnostic value of microRNA (miRNA) expression aberrations in lung cancer has been studied intensely in recent years. However, due to the application of different technological platforms and small sample size, the miRNA expression profiling efforts have led to inconsistent results between the studies. We performed a comprehensive metaanalysis of 20 published miRNA expression studies in lung cancer, including a total of 598 tumor and 528 non-cancerous control samples. Using a recently published robust rank aggregation method, we identified a statistically significant miRNA meta-signature of seven upregulated (miR-21, miR-210, miR-182, miR-31, miR-200b, miR-205 and miR-183) and eight downregulated (miR-126-3p, miR-30a, miR-30d, miR-486-5p, miR-451a, miR-126-5p, miR-143 and miR-145) miRNAs. We conducted a gene set enrichment analysis to identify pathways that are most strongly affected by altered expression of these miRNAs. We found that meta-signature miRNAs cooperatively target functionally related and biologically relevant genes in signaling and developmental pathways. We have shown that such meta-analysis approach is suitable and effective solution for identification of statistically significant miRNA meta-signature by combining several miRNA expression studies. This method allows the analysis of data produced by different technological platforms that cannot be otherwise directly compared or in the case when raw data are unavailable.

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Section: Discussionmentioning

confidence: 99%

Meta‐analysis of microRNA expression in lung cancer

Võsa

Vooder

Kolde

et al. 2012

Intl Journal of Cancer

190

127

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“…3,4 Interestingly, hsa-miR-376b was shown to be differentially expressed in a number of human cancer types, including non-small lung cancer, human uterine leiomyomas, renal cell carcinomas, and in animal experimental models of ischemia/reperfusion. 35,[43][44][45][46] Moreover, changes in the expression of DlkI/Gtl2 region and the miR-376 cluster members were observed in various types of cancers. DlkI/ Gtl2 region miRNA expression was downregulated in epithelial ovarian cancers 47 but samples showing incomplete response to platinum-based treatment had higher 376c expression than those with a complete response.…”

Section: Discussionmentioning

confidence: 99%

miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1

et al. 2012

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Keywords: macroautophagy, mammalian autophagy regulation, microRNA, hsa-miR-376b, BECN1, Beclin 1, ATG4C, drug research Abbreviations: miRNA, microRNA; PtdIns(3)P, phosphatidylinositol 3-phosphate; MAP1LC3, LC3, microtubule-associated protein 1 light chain 3; RISC, RNA-induced silencing complexes; miR-376b, hsa-miR-376b; MRE, miRNA responsive element Macroautophagy (autophagy) is the major intracellular degradation pathway for long-lived proteins and organelles. It helps the cell to survive a spectrum of stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Moreover, abnormalities of autophagy play a role in major health problems including cancer and neurodegenerative diseases. Yet, mechanisms controlling autophagic activity are not fully understood. Here, we describe hsa-miR-376b (miR-376b) as a new microRNA (miRNA) regulating autophagy. We showed that miR-376b expression attenuated starvation-and rapamycin-induced autophagy in MCF-7 and Huh-7 cells. We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. miR-376b target sequences were present in the 39 UTR of ATG4C and BECN1 mRNAs and introduction of mutations abolished their miR-376b responsiveness. Antagomir-mediated inactivation of the endogenous miR-376b led to an increase in ATG4C and BECN1 levels. Therefore, miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.

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“…Of note, racial differences in miRNA expression have been observed in several studies. Son et al found that miRNA expression profiles in non-small cell lung cancer were different between Korean and Western populations [16]. In another study, a number of miRNAs were significantly differentially expressed in uterine leiomyoma between AA and EA women [17].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in microRNAs and breast cancer risk in African American and European American women

Yao

Graham

Shen

et al. 2013

Breast Cancer Res Treat

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MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in 6 miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women’s Circle of Health Study (WCHS). Allele frequencies of most SNPs (87%) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51% increased risk in AAs (OR=1.51, 95% CI=1.30–1.74, p=3.3*10−8) and a 73% increased risk in EAs (OR=1.73, 95% CI=1.45–2.06, p=1.4*10−9). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.

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MicroRNA Expression Profiles in Korean Non-Small Cell Lung Cancer

Cited by 16 publications

References 37 publications

Meta‐analysis of microRNA expression in lung cancer

Meta‐analysis of microRNA expression in lung cancer

miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1

Genetic variants in microRNAs and breast cancer risk in African American and European American women

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