Abstract
MicroRNA (miRNAs) is a group of small non-coding 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 five-year 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.
1 Introduction
Lung cancer results in more deaths than any other cancer, including breast, colon and prostate tumors. According to clinic pathology, lung cancer is divided into two categories: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with NSCLC being more common around the world.
miRNAs have been identified to be closely related to cancer research and as of 2015, there were over 2500 miRNAs described in the human genome miRBase [1]. Generally, the function of miRNAs in cancer has been divided into two categories: oncogenic or tumor suppressor miRNAs. The miRNAs with oncogenic functions inhibit mRNA during post-transcription and then lower the protein levels of molecules with tumor suppressor functions. Conversely, miRNAs with tumor suppressors may also target DNA methytransferases (DNMT) 3A and 3B except for mRNA and protein [2]. Meanwhile, cell and tissue context as well as the physiological and pathophysiological states have a substantial influence on gene expression when miRNAmediated. For cancer production and development, uncontrolled cell proliferation is undoubtedly an essential step and during this process aberrant miRNAs expression has a great influence on tumor cell growth [3]. This article will discuss how miRNAs acts as a mediator in lung cancer suppression and oncogenesis.
2 Oncogenesis miRNAs in lung cancer
When compared to adjacent normal lung tissue, oncogenic miRNAs are defined by a higher expression of miRNAs in the malignant lung tissues. Takahashi[4] found that the miRNA-17~92 cluster specifically is markedly overexpressed in lung cancer cells and is related to enhanced cell growth [4]. miRNA profiling studies [5] have also revealed which members are overexpressed in this cluster. When miR-17-5 p and miR-20a are inhibited along with antisense oligonucleotides, miRNA-17~92 – which is overexpressed in lung cancer – will induce selective apoptosis. This suggests an oncogenic function of miRNA-17~92 [6]. Transactivation by E2F family members [7] and MYC [8] also has a close relationship with miRNA-17 ~ 92 expressions. MYC is generally overexpressed in SCLC [9] and HIF-1a – as one of direct targets of miRNA-17~92 – is downregulated by MYC [10]. This relationship further suggests that miRNA-17~92 affects cell proliferation of lung cancer. SBC-3, a SCLC cell line, has been examined using the proteomic approach to identify other targets of miRNA-17~92, one of which is the RAS-related protein 14 (RAB14), which induces surfactant secretion in the lungs [11]. A related study showed that miRNA-17~92 could induce RAB14 downregulation, which may could therefore lead to lung tissue that is sensitive to external carcinogens [11].
Some oncogenic miRNAs are identified as potential prognostic biomarkers and these include miR-92a-2 in SCLC [12] and miR-155, miR-30e-3p, miR-130a and let-7f in NSCLC [13–15]. Among oncogenic miRNAs, miR-21 is especially noteworthy, as Zhu et al. illustrated that it may induce the downregulation of specific sets of target genes to facilitate tumor invasion and metastasis [16]. This process involves the expression products of pro-apoptotic genes such as Apaf1, Faslg, Pdcd4 and RhoB [17,18].
Another promising anti-tumor target is the Apo2L/ TNF-α-related apoptosis-inducing ligand (TRAIL), which is a member of the recently identified TNF family [19]. It is reported that when miR-221/222 was upregulated in NSCLC, TRAIL was resisted [19]. Two genes Kit and p27Kipl are related to this kind of regulation and a study has revealed that a decrease in the level of p27Kip1 seems to explain a decreased sensitivity to TRAIL-related apoptosis [20].
It is reported that miR-494 is upregulated when human bronchial epithelial cells are transformed by a chemical carcinogen [21], suggesting that miR-494 acts as an oncogenic miRNA by inhibiting apoptosis of cancer cells. Meanwhile, miR-328 is generally overexpressed in lung tumor patients with brain metastases due to it promoting cell migration [22]. Inhibition of miR-301 hosted in the SKA2 gene could induce an increase of cell proliferation and invasion through the ERK/CREB pathway by promoting colony formation and the mitotic index [23]. miR-93, miR-98 and miR-197 could directly downregulate FUSI gene with tumor suppressive activity, which promotes lung cancer growth [24]. Furthermore, miR-106 and miR-150 influence the regulation in lung cancer cell growth and apoptosis by targeting RB and TP53 respectively [25].
2.1 Tumor suppressive miRNAs in lung cancer
Contrary to oncogenic miRNAs, tumor suppressive miRNAs are normally suppressed in lung cancer. For example, of the earliest known miRNAs, let-7, shows suppression in bronchioloalveolar carcinoma [26] and lung adenocarcinoma [27,28]. As members of the let-7 family, let-7a-1, 7a-2,7a-3,7b,7c,7d,7e,7f-1,7f-2,7g,7i, miR-98 and miR-202 were subsequently uncovered in C. elegans [29,30]. The miR-34/449 family however were found to control apoptosis and cell cycle arrest in lung cancer cell lines by directly regulating transcription factors p53 and E2F [31,32]. As an example, inactivated miR-34a may cause transcription silence in lung cancer through CpG methylation, which indicates that miR-34a may be used as a biomarker for NSCLC [33,34]. Based on these directly targeted genes, miRNAs of miR-34/49 are categorized into four classes: (a) targeting CDK4/6, c-MYC, E2Fs, CCNE2 and MET for arresting cell cycle; (b) targeting c-MYC, SIRT1 and HDMX for activating senescence; (c) targeting BCL-2, N-MYC, HDACI and MET for rendering apoptosis; and (d) targeting SERPINE1, AXL, SNAIL1 and HMGA2 [35–38].
miR-15a and miR-16-1 together with miR-15b and miR-16-2 belong to the cluster of miR-15/16, and when the deletion or downregulation of miR-15 and miR-16 occurs, many phases of lung cancer development – including proliferation, invasion and cell survival – are inhibited [39]. This phenomenon suggests their role as tumor suppressors. The regulation progression however does involve many genes, including BCL-2, CCND1, ETS1, JUN, MSH2 and WNT3A [40].
Located at chromosome 1 and chromosome 12, miR-200 acts as an inhibitor in epithelial-mesenchymal transition (EMT) by targeting ZEB1 and ZEB2 [41]. This highlights the role of miR-200 in the regulation of cancer pathogenesis by facilitating the invasion and metastasis of lung cancers. Previous work has revealed that upregulation of miR-200 in lung tumor cells prevents cancer cells going through EMT, thus weakening the potential for cellular invasion and metastasis [42]. miR-205 is another suppressor miRNA that has the same mechanism as miR-200 [43]. A recent study suggests that miR-205 together with miR-200 downregulate GATA3, which is a component of Notch signaling in promoting metastatic colonization to the lung [44] and sensitivity of lung cancer cells to multidrug [45].
In humans, miR-143 and miR-145 are located on chromosome 5 [46]. 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 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, NUDTI, EGFR and OCT4 [48].
miR-29 plays an indirect role in the inhibition of tumorigenicity through demethylation by DNA methyltransferases DNMT3A and -3B [49]. miR-126 has also been identified as an important inhibitory factor of vascular proliferation via the suppression of vascular epithelial growth factor (VEGF) [50]. Therefore miR-126 is identified as a tumor suppressor because it will be downregulated in cases of lung cancer [51].
There are three miRNAs, miR-1, miR-133 and miR-206, which are highly expressed in cardiac and smooth muscle tissues and, have been found to exhibit cancer suppressive activities [52]. miR-1 appears to have some role in the inhibition of cell growth, tumorigenicity and clonogenic survival when it is downregulated [53]. This likely involves many target genes, including MET, PIM-1 and FOXPI. miR-133a meanwhile has higher levels of expression in lung squamous cell carcinomas [54]. The expression of miR-206 is lower in metastatic tumors and thus when it is inhibited, cell proliferation, invasion and migration may be motivated [55].
2.2 Some miRNAs that show both oncogenic and suppression actions on lung cancer
In different contexts, individual miRNAs may show both oncogenic and suppressive actions in lung cancer.
miR-31, located on chromosome 9, can be induced by carcinogens in lung tissue[56] and has been shown to acts as an oncogenic in mouse and human lung cancer [57]. After potential target genes were uncovered via bioinformatic analysis, two tumor suppressor genes were found: LAST2 and PPP2R2A [58]. Further, when targeting ITGA5, RDX and RhoA, miR-31 may induce the recession of cancer cell metastasis and show suppressive tendencies [59].
In 2008, miR-7 was identified as a suppressive miRNA in tumors [60]. miR-7 acts in this suppressor role by targeting EGFR and BCL-2, along with downregulation of the AKT pathway which inhibits the viability and growth of cancer cells [61]. On the contrary however, targeting EGFR as well as PAS/ERK/MYC pathway induces miR-7 expression, which promotes proliferation and tumorigenicity [62].
miR-125 has two different members, miR-125a and miR-125b. In 2007, the miR-125 family was identified as a tumor suppressor via the downregulation of the ERBB2 and ERBB3 genes [63]. On the other hand, miR-125a/b also show oncogenic behavior due to the targeting of TP53 [64].
3 Future directions of miRNAs of lung cancer
The study of miRNAs is a promising method to improve the accuracy of diagnosis, classification and clinical prognostic information for lung cancer cases. However, it is necessary to match the miRNA feature to the corresponding subtype of lung cancer. For targeted therapies, miRNA profiles may help to predict patient response. Even for people not suffering from lung cancer, miRNA profiles might identify those individuals with a higher risk of developing of lung cancer, which may then enable them to alter their lifestyle.
Currently, in order to analyze the necessary miRNA expression, genetically-engineered mouse models of lung cancer have been established which simulate patients. 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. Generally, chemically-modified RNA analogs are remarkable therapeutic agents. These RNA analogs have the advantage that they minimize off-target 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.
4 Conclusion
As the most common cause of cancer mortality, the development of lung cancer is closely tied to miRNAs. It is therefore necessary to harness the full knowledge so far uncovered about the role of miRNAs in regulating gene expression in lung cancer. The primary challenge for miRNA therapy however is improving the control of delivery; especially in relation to therapy stability and off-target effects. Nonetheless, further improvements in the treatment of lung cancer are undoubtedly urgent. Current studies will give us information as to whether miRNA strategies could be used alone or in combination with chemotherapy to improve the specificity and efficacy of current treatments.
Abbreviations
AKT v-akt murine thymoma viral oncogene homolog
AXL AXL receptor tyrosine kinase
BCL-2 B-cell CLL/lymphoma 2
CCND1 cyclin D1
CCNE2 cyclin E2
CDK4 cyclin-dependent kinase 4
CDK6 cyclin-dependent kinase 6
c-MYC v-myc myelocytomatosis viral oncogene homolog
E2F E2F transcription factor 1
EGFR epidermal growth factor receptor
ERBB2/3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2/3
ETS1 v-ets erythroblastosis virus E26 oncogene homolog 1
FUS1 fused in sarcoma
HDMX Mdm2 p53 binding protein homolog
HIF-1α hypoxia inducible factor 1, alpha subunit
HMGA2 high mobility group AT-hook 2
ITGA5 integrin, alpha 5
MET met proto-oncogene
MSH2 mutS homolog 2
NUDT1 nudix (nucleoside diphosphate linked moiety X)-type motif 1
OCT4 POU class 5 homeobox 1
PPP2R2A protein phosphatase 2 regulatory subunit B alpha
SERPINE1 serpin peptidase inhibitor clade E
SIRT1 sirtuin 1
SNAIL1 snail homolog 1
TP53 p53 tumor suppressor
WNT3A wingless-type
Conflict of interest: Authors declare nothing to disclose.
References
1 Kozomara A., Griffiths-Jones S., miRBase: annotating high confidence microRNAs using deep sequencing data, Nucleic Acids Res., 2014, 42, 68-73.10.1093/nar/gkt1181Search in Google Scholar PubMed PubMed Central
2 Xin W., Melissa G., Piper H., Melissa C., Gerard J.N, Clay B.M., et al., MicroRNAs in the Pathogenesis of Lung Cancer, Thorac. Oncol., 2009, 4, 1028-1034.10.1097/JTO.0b013e3181a99c77Search in Google Scholar PubMed PubMed Central
3 Zhang B., Pan X., Cobb G. P., Anderson T. A., MicroRNAs as oncogenes and tumor suppressors, Develop. Biol., 2007, 302, 1-12.10.1016/j.ydbio.2006.08.028Search in Google Scholar PubMed
4 Hayashita Y., Osada H., Tatematsu Y., Yamada H., Yanagisawa N., Tomida S., et al., A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation, Cancer Res., 2005, 65, 9628-9632.10.1158/0008-5472.CAN-05-2352Search in Google Scholar PubMed
5 Volinia S., Calin G.A., Liu C.G., Ambs S., Cimmino A., Petrocca F., et al., A microRNA expression signature of human solid tumors defines cancer gene targets, Proc. Natl. Acad. Sci. USA, 2006,103,2257-2261.10.1073/pnas.0510565103Search in Google Scholar PubMed PubMed Central
6 Matsubara H., Takeuchi T., Nishikawa E., Yanagisawa K., Hayashita Y., Ebi H., et al., Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92, Oncogene, 2007, 26, 6099-6105.10.1038/sj.onc.1210425Search in Google Scholar PubMed
7 Sylvestre Y., De Guire V., Querido E., Mukhopadhyay U.K., Bourdeau V., Major F., An E2F/miR-20a autoregulatory feedback loop, J. Biol. Chem., 2007, 282, 2135-2143.10.1074/jbc.M608939200Search in Google Scholar PubMed
8 Donnell K.A., Wentzel E.A., Zeller K.I., Dang C.V., Mendell J.T., c-Myc-regulated microRNAs modulate E2F1 expression, Nature, 2005,435,839-843.10.1038/nature03677Search in Google Scholar PubMed
9 Takahashi T., Obata Y., Sekido Y., Hida T., Ueda R., Watanabe H., et al., Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics, Cancer Res., 1989, 49, 2683-2688.Search in Google Scholar
10 Taguchi A., Yanagisawa K., Tanaka M., Cao K., Matsuyama Y., Goto H., et al., Takahashi T., Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res., 2008, 68, 5540-5545.10.1158/0008-5472.CAN-07-6460Search in Google Scholar PubMed
11 Kanzaki H., Ito S., Hanafusa H., Jitsumori Y, Tamaru S., Shimizu K., et al., Identification of direct targets for the miR-17-92 cluster by proteomic analysis. Proteomics, 2011, 11, 3531-3539.10.1002/pmic.201000501Search in Google Scholar PubMed
12 Ranade A.R., Cherba D., Sridhar S., MicroRNA 92a-2*: a biomarker predictive for chemoresistance and prognostic for survival in patients with small cell lung cancer, J. Thorac. Oncol., 2010, 5, 1273-1278.10.1097/JTO.0b013e3181dea6beSearch in Google Scholar PubMed
13 Yanaihara N., Caplen N., Bowman E., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell, 2006, 9, 189-198.10.1016/j.ccr.2006.01.025Search in Google Scholar PubMed
14 Wang X.C., Tian L.L., Wu H.L., Expression of miRNA-130a in nonsmall cell lung cancer, Am. J. Med. Sci., 2010, 5, 385-388.10.1097/MAJ.0b013e3181e892a0Search in Google Scholar PubMed
15 Silva J., Garcia V., Zaballos A., Vesicle-related microRNAs in plasma of NSCLC patients and correlation with survival. Eur. Respir.J, 2011, 37, 617-623.10.1183/09031936.00029610Search in Google Scholar PubMed
16 Ren L., Huang C., Liu Y. H., Yu Y., Lin L., Wen L. J., The effect and mechanism of microRNA-21 on cis-dichlorodiamineplatinum resistance in lung cancer cell strain, Zhonghua Yi Xue Za Zhi, 2016,96,1454-1458.Search in Google Scholar
17 Zhu S.,Wu H., Wu F., Nie D., Sheng S., Mo Y.Y, et al., MicroRNA-21 targets tumor suppressor genes in invasion and metastasis, Cell Res., 2008, 18, 350-359.10.1038/cr.2008.24Search in Google Scholar PubMed
18 Hatley M.E., Patrick D.M., Garcia M.R., Modulation of K-Ras- dependent lung tumorigenesis by microRNA-21, Cancer Cell, 2010,18,282-293.10.1016/j.ccr.2010.08.013Search in Google Scholar PubMed PubMed Central
19 Schaefer U., Voloshanenko O., Willen D., Walczak H., TRAIL: a multifunctional cytokine, Front Biosci., 2007, 12, 3813-3824.10.2741/2354Search in Google Scholar PubMed
20 Garofalo M., Quintavalle C., Di L.G., Zanca C., Romano G., Taccioli C., MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer, Oncogene, 2008, 27, 3845-3855.10.1038/onc.2008.6Search in Google Scholar PubMed
21 Liu L., Jiang Y., Zhang H., Greenlee A.R., Han Z., Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a) pyrene-trans-7,8-dihydrodiol- 9,10-epoxide, Life Sci., 2010, 86,192-198.10.1016/j.lfs.2009.12.002Search in Google Scholar PubMed
22 Arora S., Ranade A.R., Tran N.L., Nasser S., Sridhar S., Korn R.L., et al., MicroRNA-328 is associated with (nonsmall) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration, Int. J. Cancer, 2011, 129, 2621-2631.10.1002/ijc.25939Search in Google Scholar PubMed PubMed Central
23 Cao G., Huang B., Liu Z., Zhang J., Xu H.,Xia W., et al., Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways , Biochem. Biophys. Res. Commun., 2010, 396, 978-982.10.1016/j.bbrc.2010.05.037Search in Google Scholar PubMed
24 Du L., Schageman J.J., Subauste M.C., Saber B., Hammond S.M., Prudkin L., et al., miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1, Mol. Cancer Res., 2009,7,1234-1243.10.1158/1541-7786.MCR-08-0507Search in Google Scholar PubMed PubMed Central
25 Wang P.Y, Li Y.J, Zhang S., Li Z.L., Yue Z., Xie N., et al., Regulating A549 cells growth by ASO inhibiting miRNA expression, Mol. Cell Biochem., 2010, 339,163-711.10.1007/s11010-009-0380-2Search in Google Scholar PubMed
26 Inamura K., Togashi Y., Nomura K., let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis, Lung Cancer, 2007, 58, 392-396.10.1016/j.lungcan.2007.07.013Search in Google Scholar PubMed
27 Yanaihara N., Caplen N., Bowman E., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell, 2006, 9,189-198.10.1016/j.ccr.2006.01.025Search in Google Scholar PubMed
28 Takamizawa J., Konishi H., Yanagisawa K., Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival, Cancer Res., 2004, 64, 3753-3756.10.1158/0008-5472.CAN-04-0637Search in Google Scholar PubMed
29 Reinhart B.J., Slack F.J., Basson M., Pasquinelli A.E., Bettinger J.C., Rougvie A.E., The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans, Nature, 2000,403,901-906.10.1038/35002607Search in Google Scholar PubMed
30 Pasquinelli A.E., Reinhart B.J., Slack F., Martindale M.Q., Kuroda M.I., Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA, Nature, 2000,408,86-89.10.1038/35040556Search in Google Scholar PubMed
31 Chang T.C., Wentzel E.A., Kent O.A., Ramachandran K., Mullendore M., Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis, Mol. Cell., 2007, 26, 745-752.10.1016/j.molcel.2007.05.010Search in Google Scholar PubMed PubMed Central
32 Raver S.N., Marciano E., Meiri E., Spector Y, Rosenfeld N., Moskovits N., et al., Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, Mol. Cell., 2007, 26, 731-743.10.1016/j.molcel.2007.05.017Search in Google Scholar PubMed
33 Gallardo E., Navarro A., Vinolas N., MiR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer, Carcinogenesis, 2009, 30,1903-1914.10.1093/carcin/bgp219Search in Google Scholar PubMed
34 Lodygin D., Tarasov V., Epanchintsev A., Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer, Cell Cycle, 2008, 7, 2591-2600.10.4161/cc.7.16.6533Search in Google Scholar PubMed
35 Lize M., Klimke A., Dobbelstein M., MicroRNA-449 in cell fate determination, Cell Cycle, 2011,10, 2874-2882.10.4161/cc.10.17.17181Search in Google Scholar PubMed
36 Kim N.H., Kim H.S., Li X.Y., Lee I., Choi H.S., Kang S.E., et al., A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition, J. Cell Biol., 2011,195, 417-433.10.1083/jcb.201103097Search in Google Scholar PubMed PubMed Central
37 Mudduluru G., Ceppi P., Kumarswamy R., Scagliotti G.V., Papotti M., Allgayer H., et al., Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer., Oncogene, 2011, 30, 2888-2899.10.1038/onc.2011.13Search in Google Scholar PubMed
38 Muth M., Hussein K., Jacobi C., Kreipe H., Bock O., Hypoxiainduced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA – a mechanism involved in SERPINE1 (PAI-1) overexpression, J. Transl. Med., 2011, 9-24.10.1186/1479-5876-9-24Search in Google Scholar PubMed PubMed Central
39 Aqeilan R.I., Calin G.A., Croce C.M., miR-15a and miR-16-1 in cancer: discovery, function and future perspectives, Cell Death Differ., 2010, 17, 215-220.10.1038/cdd.2009.69Search in Google Scholar PubMed
40 Gregory P.A., Bert A.G., Paterson E.L., Barry S.C., Tsykin A., Farshid G., et al., The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1, Nat. Cell Biol., 2008,10, 593-601.10.1038/ncb1722Search in Google Scholar PubMed
41 Ofir M., Hacohen D., Ginsberg D., MiR-15 and miR-16 are direct transcriptional targets of E2F1 that limit E2F-induced proliferation by targeting cyclin E, Mol. Cancer Res., 2011, 9, 440-447.10.1158/1541-7786.MCR-10-0344Search in Google Scholar PubMed
42 Gibbons D.L., Lin W., Creighton C.J., Rizvi Z.H., Gregory P.A., Goodall G.J., et al., Thilaganathan N., Du L., Zhang Y., Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression, Genes Dev., 2009, 23, 2140-2151.10.1101/gad.1820209Search in Google Scholar PubMed PubMed Central
43 Goodarzi H., Hua Y., Wei Y., Hu G., Garcia B.A., Ragoussis J., Amadori D., Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization, Nat. Med., 2011, 17,101-108.10.1038/nm.2401Search in Google Scholar PubMed PubMed Central
44 Zhu W., Xu H., Zhu D., Zhi H., Wang T., Wang J., et al., miR-200bc/429 cluster modulates multidrug resistance of human cancer cell lines by targeting BCL2 and XIAP, Cancer Chemother. Pharmacol., 2011, DOI: 10.1007/s00280-011-1752-3.Search in Google Scholar
45 Xin M., Small E.M., Sutherland L.B., Qi X., McAnally J., Plato C.F., et al., MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury, Genes Dev., 2009, 23, 66-78.10.1101/gad.1842409Search in Google Scholar PubMed PubMed Central
46 Izzotti A., Calin G.A., Arrigo P., Steele V.E., Croce C.M., De F.S., et al., Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke, FASEB J., 2009, 23,6-12.10.1096/fj.08-121384Search in Google Scholar PubMed PubMed Central
47 Liu X., Sempere L.F., Galimberti F., Freemantle S.J., Black C., Dragnev K.H., et al., Uncovering growth-suppressive MicroRNAs in lung cancer. Clin. Cancer Res., 2009,15,1177-1183.10.1158/1078-0432.CCR-08-1355Search in Google Scholar PubMed PubMed Central
48 Cho W.C., Chow A.S., Au J.S., MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1, RNA Biol., 2011, 8, 5-31.10.4161/rna.8.1.14259Search in Google Scholar PubMed
49 Fabbri M., Garzon R., Cimmino A., Liu Z., Zanesi N., Callegari E., Liu S., et al., MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. USA, 2007,104,15, 805-810.10.1073/pnas.0707628104Search in Google Scholar PubMed PubMed Central
50 Gao W., Shen H., Liu L., Xu J., Shu Y., MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis, J. Cancer Res. Clin. Oncol., 2010, 137, 557-566.10.1007/s00432-010-0918-4Search in Google Scholar PubMed
51 Yang Y., Li X., Yang Q., Wang X., Zhou Y., Jiang T., et al., The role of microRNA in human lung squamous cell carcinoma, Cancer Genet. Cytogenet, 2010, 200,127-133.10.1016/j.cancergencyto.2010.03.014Search in Google Scholar PubMed
52 Chen J.F., Mandel E.M., Thomson J.M., Wu Q., Callis T.E., Hammond S.M., et al., The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation, Nat. Genet., 2006, 38, 228-233.10.1038/ng1725Search in Google Scholar PubMed PubMed Central
53 Nasser M.W., Datta J., Nuovo G., Kutay H., Motiwala T., Majumder S., et al., Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1, J. Biol. Chem., 2008, 283, 33, 394-405.10.1074/jbc.M804788200Search in Google Scholar PubMed PubMed Central
54 Wang X., Ling C., Bai Y., Zhao J., MicroRNA-206 is associated with invasion and metastasis of lung cancer, Anat. Rec. (Hoboken), 2010, 294, 88-92.10.1002/ar.21287Search in Google Scholar PubMed
55 Moriya Y., Nohata N., Kinoshita T., Mutallip M., Okamoto T., Yoshida S., et al., Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma, J. Hum. Genet., 2012, 57, 38-45.10.1038/jhg.2011.126Search in Google Scholar PubMed
56 Xi S., Yang M., Tao Y., Xu H., Shan J., Inchauste S., Zhang M., Mercedes L, Cigarette smoke induces C/EBP-beta-mediated activation of miR-31 in normal human respiratory epithelia and lung cancer cells., PLOS One, 2010, 5,100-120.10.1371/journal.pone.0013764Search in Google Scholar PubMed PubMed Central
57 Liu X., Sempere L.F., Ouyang H., MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors, J. Clin. Invest., 2010, 120,1298-1309.10.1172/JCI39566Search in Google Scholar PubMed PubMed Central
58 Liu X., Sempere L.F., Ouyang H., Memoli V.A., Andrew A.S., Luo Y., et al., MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors, J. Clin. Inves., 2010,120,1298-1309.10.1172/JCI39566Search in Google Scholar
59 Valastyan S., Chang A., Benaich N., Reinhardt F., Weinberg R.A., Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis, Cancer Res., 2010; 70, 5147-5154.10.1158/0008-5472.CAN-10-0410Search in Google Scholar PubMed PubMed Central
60 Kefas B., Godlewski J., Comeau L., Li Y., Abounader R., Hawkinson M., et al., Fine H., Chiocca E.A., Lawler S., Purow B. microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res., 2008, 68, 3566-3572.10.1158/0008-5472.CAN-07-6639Search in Google Scholar PubMed
61 Webster R.J., Giles K.M., Price K.J., Zhang P.M., Mattick J.S., Leedman P.J., Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7, J. Biol. Chem., 2009,284,5731-5741.10.1074/jbc.M804280200Search in Google Scholar PubMed
62 Chou Y.T., Lin H.H., Lien Y.C., Wang Y.H., Hong C.F., Kao Y.R., et al., EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF, Cancer Res., 2010, 70, 8822-8831.10.1158/0008-5472.CAN-10-0638Search in Google Scholar PubMed
63 Scott G.K., Goga A., Bhaumik D., Berger C.E., Sullivan C.S., Benz C.C, et al., Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b, J. Biol. Chem, 2007, 282,1479-1486.10.1074/jbc.M609383200Search in Google Scholar PubMed
64 Nagayama K., Kohno T., Sato M., Arai Y., Minna J.D., Yokota J., et al., Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution, Genes Chromosomes Cancer, 2007, 46, 1000-1010.10.1002/gcc.20485Search in Google Scholar PubMed
65 Liu X., Sempere L.F., Galimberti F., Uncovering growth- suppressive MicroRNAs in lung cancer, Clin Cancer Res., 2009, 15,1177-1183.10.1158/1078-0432.CCR-08-1355Search in Google Scholar PubMed PubMed Central
© 2016 Suning Zhang, Zongang Liu
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
