Uncovering Growth-Suppressive MicroRNAs in Lung Cancer

Liu, Xi; Sempere, Lorenzo F.; Galimberti, Fabrizio; Freemantle, Sarah J.; Black, Candice C.; Dragnev, Konstantin H.; Ma, Yan; Fiering, Steven; Memoli, Vincent A.; Li, Hua; DiRenzo, James; Korc, Murray; Cole, Charles N.; Bak, Mads; Kauppinen, Sakari; Dmitrovsky, Ethan

doi:10.1158/1078-0432.ccr-08-1355

Cited by 165 publications

(170 citation statements)

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“…In the present study, the expression levels of hsa-miR-34-c, hsa-miR-126 and hsa-miR-145 were downregulated, while the expression levels of hsa-miR-183 was upregulated (Table II). The targets of hsa-miR-34, cyclin E and p53, are associated with the cell cycle and tumor formation (26,27); the low expression of hsa-miR-34 may result in upregulation of cyclin E and p53, which is crucial in the development of SCLC. The epidermal growth factor receptor (EGFR) encoded by the target of hsa-miR-145 may inhibit cancer growth (28); the downregulation of hsa-miR-145 in SCLC may generate an increase in the expression levels of EGFR and thus promote cancer growth.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification and expression analysis of microRNA involved in small cell lung cancer via deep sequencing

Yan

Shi

Wang

et al. 2014

Molecular Medicine Reports

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Abstract. Small cell lung cancer is a major cause of mortality worldwide. microRNAs (miRNAs) are involved in various biological processes through regulating gene expression. In the present study, to identify the miRNAs involved in human small cell lung cancer at the genome-wide level, Solexa sequencing was employed to sequence two small RNA (sRNA) libraries from small cell lung cancer tissues (LC sRNA library) and the corresponding normal tissues (NT sRNA library). Deep sequencing of the two sRNA libraries identified a number of conserved miRNAs and differential expression analysis of these miRNAs revealed 81 miRNAs differentially expressed in small cell lung cancer, of which more than half were downregulated. The expression trends determined by sequencing were validated by reverse transcription-quantitative polymerase chain reaction analysis. The annotations for the targets of these miRNAs were predicted. This study provides valuable information for understanding the regulatory mechanisms of miRNAs involved in human small cell lung cancer. IntroductionMicroRNAs (miRNAs) are small non-coding RNA molecules, ~22 nucleotides long, which are widely distributed in plants and animals (1,2). The primary miRNA transcripts are cleaved by Drosha and Dicer enzymes to form mature miRNAs, which serve as posttranscriptional negative gene regulators by either cleaving mRNA or inhibiting translation (3,4). Through such mechanisms, miRNAs are involved in various biological processes, including organ development, tissue differentiation, cell cycle regulation and cancer development (4-6).Lung cancer is the predominant cause of cancer-related mortality worldwide and its pathogenesis is closely associated with tobacco smoking. Lung cancer is categorized into two main histological groups: Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Regulation of miRNAs is closely associated with tumor initiation, promotion and progression (7). Recently, increasing evidence has demonstrated that miRNAs may be associated with lung cancer. A previous study revealed that an increase in hsa-miR-196a expression levels was a characteristic molecular change in NSCLC (8,9), and that hsa-miRNA-196a promoted NSCLC cell proliferation and invasion via targeting HOXA5 (10). Overexpression of miR-200 was shown to reduce the expression levels of NSCLC prognostic biomarkers in H1299 and BEAS-2B cells (11). miR-449a, which inhibited migration and invasion through targeting c-Met, was found to be downregulated in NSCLC tissues and cell lines (12). Reduced expression of miR-101 was associated with overexpression of EZH2 and exhibited tumor-suppressive functions in NSCLC (13). This evidence suggests that miRNAs are crucial in NSCLC; however, little is known regarding the functions and regulation of miRNAs in SCLC.In the present study, Solexa sequencing was used to generate a large quantity of small RNA (sRNA) data for SCLC and corresponding normal tissues. Sequence analysis was employed to identify specific miRNAs associated with SCLC and these ...

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Section: Discussionmentioning

confidence: 99%

Genome-wide identification and expression analysis of microRNA involved in small cell lung cancer via deep sequencing

Yan

Shi

Wang

et al. 2014

Molecular Medicine Reports

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“…Previous work has shown that miR-143 and miR-145 expression levels are downregulated in rodent lungs exposed to cigarette smoke (which is a severe carcinogen) [46]. Additional studies have shown Brought to you by | MIT Libraries Authenticated Download Date | 5/9/18 9:15 AM that miR-143 and miR-145 have an inhibitory effect on lung cancer cell growth in both mice and humans [47]. This regulation progress involves many target genes, such as C-MYC, NUDT1, EGFR and OCT4 [48].…”

Section: Tumor Suppressive Mirnas In Lung Cancermentioning

confidence: 99%

“…Accordingly, when a miRNA is identified as a candidate for tumor suppression or oncogenesis, its function will be confirmed by gain/loss studies of miRNA in the established model [65]. Then, when a specific miRNA is found to play an important role in lung cancer development, specific targeting to reduce lung carcinogenesis within the same species will be attempted.…”

Section: Future Directions Of Mirnas Of Lung Cancermentioning

confidence: 99%

“…Generally, chemically-modified RNA analogs are remarkable therapeutic agents. These RNA analogs have the advantage that they minimize offtarget toxicity and so far been well tolerated in clinical studies [65]. Of course, there are possible disadvantages to this too, in is that the deregulation of a single targeted miRNA may induce global changes in gene expression, which may lead to adverse effects or even toxicity.…”

Section: Future Directions Of Mirnas Of Lung Cancermentioning

confidence: 99%

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Effect of miRNAs in lung cancer suppression and oncogenesis

Zhang

Liu

2016

Open Life Sciences

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MicroRNA (miRNAs) is a group of small noncoding RNAs. It is involved in multiple cellular processes including proliferation, development, metabolism, differentiation and apoptosis; many of which are linked to several pathological conditions, including cancer. Lung cancer is one of the leading causes of mortality in the world: in 2008 for example, there were 163,000 deaths as a result of lung cancer. Despite technologies emerging which provide the potential for novel targeted therapies and improved early diagnoses, the overall rate of fiveyear survival still remains at only 15%. One reason for this disappointing statistic is related to the presentation of the disease, and specifically a lack of markers for early detection. Notably, the expression of some miRNAs has been reported to be involved in the diagnosis, classification and even prognosis of lung cancer. Tumorsuppressive and oncogenic miRNAs were found in lung carcinogenesis and the biological functions of these miRNAs have been validated in transplantable lung cancer models and human paired normal-malignant lung tissue banks. Some of these tumor-suppressive and oncogenic miRNAs related to lung cancer will be reviewed here. This article will focus on emphasing miRNAs effectiveness as a biomarker in lung carcinogenesis and candidate pharmacology. Furthermore, how these findings improve our understanding of lung cancer biology and therapy will also be discussed.

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“…In a retrospective studies, cyclin E level has been the best predictor of survival comparing with canonical clinical factors (age, tumor size, nodal status, stage of disease) and biologic markers (steroids and Her-2 receptor status, ploidy, proliferation index, cyclins D1 and D3) (Keyomarsi et al, 2002;Liu et al, 2013). The known mechanisms of these elevated and constitutive expressions include cyclin E gene amplification, overexpression of its mRNA, increased expression of its protein, tumor specific proteolytic cleavage of the full length protein and altered profiles of microRNAs expression (Keyomarsi and Pardee, 1993;Porter et al, 2001;Ekholm-Reed et al, 2004;le Sage et al, 2007;Liu et al, 2009).…”

Section: Introductionmentioning

confidence: 99%