Frontiers of MicroRNA Signature in Non-small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases. Recent advancements in diagnostic tools, surgical treatments, chemotherapies, and molecular targeted therapies that improved the therapeutic efficacy in NSCLC. However, the 5-years relative survival rate of NSCLC is only about 20% due to the inadequate screening methods and late onset of clinical symptoms. Dysregulation of microRNAs (miRNAs) was frequently observed in NSCLC and closely associated with NSCLC development, progression, and metastasis through regulating their target genes. In this review, we provide an updated overview of aberrant miRNA signature in NSCLC, and discuss the possibility of miRNAs becoming a diagnostic and therapeutic tool. We also discuss the possible causes of dysregulated miRNAs in NSCLC.

[1]  J. Lai-Kwon,et al.  Moving beyond Epidermal Growth Factor Receptor resistance in metastatic non-small cell lung cancer - a drug development perspective. , 2021, Critical reviews in oncology/hematology.

[2]  Ping Zhang,et al.  CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging , 2021, International journal of nanomedicine.

[3]  Xunxia Bao,et al.  Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis , 2020, Frontiers in Oncology.

[4]  Xiaodong Zhang,et al.  miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling , 2020, Cell Death & Disease.

[5]  K. Kelnar,et al.  Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours , 2020, British Journal of Cancer.

[6]  C. Croce,et al.  miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer , 2020, Proceedings of the National Academy of Sciences.

[7]  K. Vasquez,et al.  Circulating microRNA‐590‐5p functions as a liquid biopsy marker in non‐small cell lung cancer , 2020, Cancer science.

[8]  Jian Huang,et al.  AGO2 phosphorylation by c-Src kinase promotes tumorigenesis , 2020, Neoplasia.

[9]  S. Chattopadhyay,et al.  Transferrin-decorated thymoquinone-loaded PEG-PLGA nanoparticles exhibit anticarcinogenic effect in non-small cell lung carcinoma via the modulation of miR-34a and miR-16. , 2019, Biomaterials science.

[10]  Eun Ju Kim,et al.  QKI, a miR‐200 target gene, suppresses epithelial‐to‐mesenchymal transition and tumor growth , 2019, International journal of cancer.

[11]  Deruo Liu,et al.  MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4 , 2019, Journal of cellular and molecular medicine.

[12]  B. Ji,et al.  Inhibition of miR-155 reduces impaired autophagy and improves prognosis in an experimental pancreatitis mouse model , 2019, Cell Death & Disease.

[13]  Jing Wang,et al.  ZEB1 suppression sensitizes KRAS mutant cancers to MEK inhibition by an IL17RD-dependent mechanism , 2019, Science Translational Medicine.

[14]  U. Pastorino,et al.  Circulating mir‐320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk , 2019, International journal of cancer.

[15]  M. Pan,et al.  Proliferation and Migration of Lung Cancer Could be Inhibited by Oxymatrine through the Regulation for miR-520/VEGF. , 2019, The American journal of Chinese medicine.

[16]  Yong Wang,et al.  The p53/miR-193a/EGFR feedback loop function as a driving force for non-small cell lung carcinoma tumorigenesis , 2019, Therapeutic advances in medical oncology.

[17]  Yongmei Yin,et al.  MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression , 2018, Cell proliferation.

[18]  C. Croce,et al.  miRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC , 2018, Nature Communications.

[19]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[20]  Hongzhuan Chen,et al.  Epigenetic silencing of miR-483-3p promotes acquired gefitinib resistance and EMT in EGFR-mutant NSCLC by targeting integrin β3 , 2018, Oncogene.

[21]  Hai-bo Wu,et al.  Long non‐coding RNA SNHG15 promotes CDK14 expression via miR‐486 to accelerate non‐small cell lung cancer cells progression and metastasis , 2018, Journal of cellular physiology.

[22]  K. Monastyrskaya,et al.  miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer , 2018, Molecular Cancer.

[23]  J. Hung,et al.  Hypoxic Lung-Cancer-Derived Extracellular Vesicle MicroRNA-103a Increases the Oncogenic Effects of Macrophages by Targeting PTEN , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[24]  F. Askin,et al.  Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. , 2017, Seminars in cancer biology.

[25]  Huijie Sun,et al.  MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2 , 2017, Cellular Physiology and Biochemistry.

[26]  Yan Liu,et al.  MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis , 2017, Molecular Cancer.

[27]  Fenggui Wei,et al.  Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p , 2017, Molecular Cancer.

[28]  M. Oren,et al.  let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery , 2017, Oncogene.

[29]  B. Shen,et al.  Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner , 2017, International journal of nanomedicine.

[30]  A. Brenner,et al.  Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors , 2017, Investigational New Drugs.

[31]  Hongbing Shen,et al.  Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling , 2017, Oncogene.

[32]  D. Amadori,et al.  Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers , 2016, Clinical Cancer Research.

[33]  L. Pan,et al.  MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN , 2016, Oncotarget.

[34]  Gregory J. Goodall,et al.  A network-biology perspective of microRNA function and dysfunction in cancer , 2016, Nature Reviews Genetics.

[35]  S. Gettinger,et al.  Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  K. J. Grande-Allen,et al.  ZEB1 Induces LOXL2-Mediated Collagen Stabilization and Deposition in the Extracellular Matrix to Drive Lung Cancer Invasion and Metastasis , 2016, Oncogene.

[37]  Feride Oeztuerk-Winder,et al.  miR-17-92/p38α Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression. , 2016, Cancer research.

[38]  B. Lim,et al.  Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression , 2016, Nature Communications.

[39]  Baosheng Li,et al.  miR‐134 inhibits non‐small cell lung cancer growth by targeting the epidermal growth factor receptor , 2016, Journal of cellular and molecular medicine.

[40]  Juan Wang,et al.  Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5 , 2016, Oncotarget.

[41]  Xi Chen,et al.  Tumor-suppressive miR-218-5p inhibits cancer cell proliferation and migration via EGFR in non-small cell lung cancer , 2016, Oncotarget.

[42]  Jeffrey T. Chang,et al.  MiR-26 down-regulates TNF-α/NF-κB signalling and IL-6 expression by silencing HMGA1 and MALT1 , 2016, Nucleic acids research.

[43]  Yunfeng Fu,et al.  Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development , 2016, Oncotarget.

[44]  Zhongming Zhao,et al.  MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. , 2015, The Journal of clinical investigation.

[45]  G. Calin,et al.  PDL1 Regulation by p53 via miR-34 , 2015, Journal of the National Cancer Institute.

[46]  C. Croce,et al.  MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7 , 2015, Oncotarget.

[47]  Baosen Zhou,et al.  MiR-486 as an effective biomarker in cancer diagnosis and prognosis: a systematic review and meta-analysis , 2015, Oncotarget.

[48]  C. Croce,et al.  MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer , 2015, Proceedings of the National Academy of Sciences.

[49]  M. Figlerowicz,et al.  High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer , 2015, Oncotarget.

[50]  Alexander Pertsemlidis,et al.  Genetic mutation of p53 and suppression of the miR-17∼92 cluster are synthetic lethal in non-small cell lung cancer due to upregulation of vitamin D Signaling. , 2015, Cancer research.

[51]  Jing Wang,et al.  The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers , 2015, Oncogene.

[52]  Gopal Chakrabarti,et al.  MiR-16 targets Bcl-2 in paclitaxel-resistant lung cancer cells and overexpression of miR-16 along with miR-17 causes unprecedented sensitivity by simultaneously modulating autophagy and apoptosis. , 2015, Cellular signalling.

[53]  Wenting Liu,et al.  The role of exosomes and "exosomal shuttle microRNA" in tumorigenesis and drug resistance. , 2015, Cancer letters.

[54]  O. Wolkenhauer,et al.  E2F1 induces miR‐224/452 expression to drive EMT through TXNIP downregulation , 2014, EMBO reports.

[55]  F. Jiang,et al.  Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer , 2014, Molecular Cancer.

[56]  A. Krüger,et al.  Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes , 2014, Oncogene.

[57]  Lixia Diao,et al.  Metastasis is regulated via microRNA-200/ZEB1 axis control of tumor cell PD-L1 expression and intratumoral immunosuppression , 2014, Nature Communications.

[58]  Xing Chen,et al.  MicroRNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET. , 2014, Cancer letters.

[59]  P. Verde,et al.  miR-340 inhibits tumor cell proliferation and induces apoptosis by targeting multiple negative regulators of p27 in non-small cell lung cancer , 2014, Oncogene.

[60]  D. Brown,et al.  Systemic Delivery of a miR34a Mimic as a Potential Therapeutic for Liver Cancer , 2014, Molecular Cancer Therapeutics.

[61]  R. Wang,et al.  MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating G1/S transition and apoptosis by targeting p21WAF1/CIP1 , 2014, British Journal of Cancer.

[62]  Y. Cheng,et al.  c-Myc suppresses microRNA-29b to promote tumor aggressiveness and poor outcomes in non-small cell lung cancer by targeting FHIT , 2014, Oncogene.

[63]  T. Speed,et al.  A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression , 2014, Genes & development.

[64]  X Wang,et al.  Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer , 2014, Oncogene.

[65]  N. Yang,et al.  MiRNA-218, a new regulator of HMGB1, suppresses cell migration and invasion in non-small cell lung cancer. , 2013, Acta biochimica et biophysica Sinica.

[66]  H. Hermeking,et al.  SNAIL and miR‐34a feed‐forward regulation of ZNF281/ZBP99 promotes epithelial–mesenchymal transition , 2013, The EMBO journal.

[67]  Julian Downward,et al.  Hmga2 functions as a competing endogenous RNA to promote lung cancer progression , 2013, Nature.

[68]  George A Calin,et al.  Tumour angiogenesis regulation by the miR-200 family , 2013, Nature Communications.

[69]  C. Croce,et al.  Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer , 2013, Proceedings of the National Academy of Sciences.

[70]  C. Croce,et al.  MicroRNA-31 Predicts the Presence of Lymph Node Metastases and Survival in Patients with Lung Adenocarcinoma , 2013, Clinical Cancer Research.

[71]  Minoru Terashima,et al.  KDM5B histone demethylase controls epithelial-mesenchymal transition of cancer cells by regulating the expression of the microRNA-200 family , 2013, Cell cycle.

[72]  Yan Wang,et al.  EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2 , 2013, Nature.

[73]  Carlo M. Croce,et al.  Causes and Consequences of MicroRNA Dysregulation , 2012, Cancer journal.

[74]  C. Croce,et al.  MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review , 2012, EMBO molecular medicine.

[75]  J. Sun,et al.  EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers , 2011, Nature Medicine.

[76]  Christopher A. Maher,et al.  A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition , 2011, The Journal of cell biology.

[77]  R. Agami,et al.  MicroRNA regulation by RNA-binding proteins and its implications for cancer , 2011, Nature Reviews Cancer.

[78]  Munish Kumar,et al.  Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis , 2011, Proceedings of the National Academy of Sciences.

[79]  P Barbry,et al.  miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity , 2011, Cell Death and Differentiation.

[80]  H. Osada,et al.  let‐7 and miR‐17‐92: Small‐sized major players in lung cancer development , 2011, Cancer science.

[81]  E. Olson,et al.  Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. , 2010, Cancer cell.

[82]  H. Allgayer,et al.  Loss of miR-200c Expression Induces an Aggressive, Invasive, and Chemoresistant Phenotype in Non–Small Cell Lung Cancer , 2010, Molecular Cancer Research.

[83]  Guanghai Yang,et al.  MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). , 2010, Clinica chimica acta; international journal of clinical chemistry.

[84]  Hansjuerg Alder,et al.  miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. , 2009, Cancer cell.

[85]  F. Slack,et al.  Regression of murine lung tumors by the let-7 microRNA , 2009, Oncogene.

[86]  C. Croce Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[87]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[88]  Anna M. Krichevsky,et al.  miR-21: a small multi-faceted RNA , 2008, Journal of cellular and molecular medicine.

[89]  F. Slack,et al.  A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. , 2008, Cancer research.

[90]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[91]  F. Slack,et al.  The let-7 family of microRNAs. , 2008, Trends in cell biology.

[92]  Carola Berking,et al.  Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer , 2008, Cell cycle.

[93]  A. Harris,et al.  Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma , 2008, British journal of haematology.

[94]  M. Korpal,et al.  The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2* , 2008, Journal of Biological Chemistry.

[95]  Sun-Mi Park,et al.  The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. , 2008, Genes & development.

[96]  Phillip A Sharp,et al.  Suppression of non-small cell lung tumor development by the let-7 microRNA family , 2008, Proceedings of the National Academy of Sciences.

[97]  C. Morrison,et al.  MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B , 2007, Proceedings of the National Academy of Sciences.

[98]  Ying Feng,et al.  Supplemental Data P53-mediated Activation of Mirna34 Candidate Tumor-suppressor Genes , 2022 .

[99]  L. Lim,et al.  A microRNA component of the p53 tumour suppressor network , 2007, Nature.

[100]  Moshe Oren,et al.  Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. , 2007, Molecular cell.

[101]  Peter A. Jones,et al.  Epigenetics and MicroRNAs , 2007, Pediatric Research.

[102]  M. Fraga,et al.  Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. , 2007, Cancer research.

[103]  H. Sültmann,et al.  The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. , 2007, Cancer research.

[104]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[105]  Sven Diederichs,et al.  Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. , 2006, Cancer research.

[106]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[107]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[108]  Y. Yatabe,et al.  A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. , 2005, Cancer research.

[109]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

[110]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[111]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[112]  Peter A. Jones,et al.  Epigenetics in human disease and prospects for epigenetic therapy , 2004, Nature.

[113]  Hiroyuki Tagawa,et al.  Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. , 2004, Cancer research.

[114]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[115]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[116]  B. Reinhart,et al.  Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA , 2000, Nature.

[117]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[118]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[119]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[120]  H. An,et al.  Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer. , 2016, Lung cancer.

[121]  Gang Liu,et al.  miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis. , 2016, Cancer research.

[122]  Shaolei Li,et al.  MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. , 2014, Cancer letters.

[123]  C. Croce,et al.  MicroRNAs in cancer. , 2014, Annual review of pathology.

[124]  林下 陽二 A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation , 2006 .