Abstract

The discovery of a new class of molecules, the 22-24 nucleotides long RNA, has initiated a new chapter in genetic information regulation studies. These molecules have a significant impact on the functioning of cells by means of negative regulation of expression of targeted mRNA. Special attention is given to exogenous, circulating miRNAs, whose levels of expression in different body fluids varies and can be deregulated by pathological, as well as physiological conditions. Extensive studies on the diagnostic potential of miRNAs are currently conducted. Attempts are made to determine specific profiles of miRNAs that will correlate with disease entity. The preliminary data gives hope that in the near future miRNAs will be applied as a diagnostic and prognostic biomarkers in many diseases. One of their most significant applications can be in the diagnosis of lung cancer – the most deadly form of cancer, due to its too late diagnosis. Abundant in miRNA molecules, blood and sputum constitute excellent diagnostic material for patients with lung cancer, especially those with non-small-cell lung cancer NSCLC. Easy procedures for obtaining this diagnostic material from patients and relatively easy analysis of miRNA expression, make these molecules promising in their use in diagnosis, predicting of therapy effects and prognosis for patients with NSCLC. This work presents information related to miRNA and their specific attributes. Moreover level of deregulated circulating miRNAs occurring in body fluids of patients with NSCLC is also discussed.

References

• 1. Arroyo J.D., Chevillet J.R., Kroh E.M., Ruf I.K., Pritchard C.C., Gibson D.F., Mitchell P.S., Bennett C.F., Pogosova-Agadjanyan E.L., Stirewalt D.L., Tait J.F., Tewari M.: Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. USA, 2011; 108: 5003-5008
  Google Scholar
• 2. Bach P.B., Mirkin J.N., Oliver T.K., Azzoli C.G., Berry D.A., Brawley O.W., Byers T., Colditz G.A. Gould M.K., Jett J.R., Sabichi A.L., Smith- -Bindman R., Wood D.E., Qaseem A., Detterbeck F.C.: Benefits and harms of CT screening for lung cancer: a systematic review. JAMA, 2012; 307: 2418-2429
  Google Scholar
• 3. Bianchi F., Nicassio F., Marzi M., Belloni E., Dall’olio V., Bernard L., Pelosi G., Maisonneuve P., Veronesi G., Di Fiore P.P.: A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol. Med., 2011; 3: 495-503
  Google Scholar
• 4. Calin G.A., Sevignani C., Dumitru C.D., Hyslop T., Noch E., Yendamuri S., Shimizu M., Rattan S., Bullrich F., Negrini M., Croce C.M.: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA, 2004; 101: 2999-3004
  Google Scholar
• 5. Cazzoli R., Buttitta F., Di Nicola M., Malatesta S., Marchetti A., Rom W.N., Pass H.I.: MicroRNAs derived from circulating exosomes as non-invasive biomarkers for screening and diagnosing lung cancer. J. Thorac. Oncol., 2013; 8: 1156-1162
  Google Scholar
• 6. Chen L., Jin H.: MicroRNAs as novel biomarkers in the diagnosis of non-small cell lung cancer: a meta-analysis based on 20 studies. Tumour Biol., 2014; 35: 9119-9129
  Google Scholar
• 7. Chen X., Ba Y., Ma L., Cai X., Yin Y., Wang K., Guo J., Zhang Y., Chen J., Guo X., Li Q., Li X., Wang W., Zhang Y., Wang J. i wsp.: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res., 2008; 18: 997-1006
  Google Scholar
• 8. Chen X., Hu Z., Wang W., Ba Y., Ma L., Zhang C., Wang C., Ren Z., Zhao Y., Wu S., Zhuang R., Zhang Y., Hu H., Liu C., Xu L. i wsp.: Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int. J. Cancer, 2012; 130: 1620-1628
  Google Scholar
• 9. Chu G., Zhang J., Chen X.: Serum level of microRNA-147 as diagnostic biomarker in human non-small cell lung cancer. J. Drug. Target, 2015; 10: 1-5
  Google Scholar
• 10. Croce C.M.: Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet., 2009; 10: 704-714
  Google Scholar
• 11. Didkowska J., Wojciechowska U.: Zachorowania i zgony na nowotwory złośliwe w Polsce. Krajowy Rejestr Nowotworów, Centrum Onkologii – Instytut im. Marii Skłodowskiej-Curie. http://onkologia. org.pl/k/epidemiologia/(09.04.2016)
  Google Scholar
• 12. Foss K.M., Sima C., Ugolini D., Neri M., Allen K.E., Weiss G.J.: miR- 1254 and miR-574-5p: serum-based microRNA biomarkers for early- -stage non-small cell lung cancer. J. Thorac. Oncol., 2011; 6: 482-488
  Google Scholar
• 13. Franchina T., Amodeo V., Bronte G., Savio G., Ricciardi G.R., Picciotto M., Russo A., Giordano A., Adamo V.: Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed- -based chemotherapy in advanced non-small cell lung cancer. J. Cell Physiol., 2014; 229: 97-99
  Google Scholar
• 14. Gao W., Lu X., Liu L., Xu J., Feng D., Shu Y.: MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer. Cancer Biol. Ther., 2012; 13: 330-340
  Google Scholar
• 15. Gibbings D.J., Ciaudo C., Erhardt M., Voinnet O.: Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell Biol., 2009; 11: 1143-1149
  Google Scholar
• 16. Gilad S., Meiri E., Yogev Y., Benjamin S., Lebanony D., Yerushalmi N., Benjamin H., Kushnir M., Cholakh H., Melamed N., Bentwich Z., Hod M., Goren Y., Chajut A.: Serum microRNAs are promising novel biomarkers. PLoS One, 2008; 3: e3148
  Google Scholar
• 17. Han L., Zhang G., Zhang N., Li H., Liu Y., Fu A., Zheng Y.: Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer. Med. Oncol., 2014; 31: 129
  Google Scholar
• 18. Hennessey P.T., Sanford T., Choudhary A., Mydlarz W.W., Brown D., Adai A.T., Ochs M.F., Ahrendt S.A., Mambo E., Califano J.A.: Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One, 2012; 7: e32307
  Google Scholar
• 19. Hu Z., Chen X., Zhao Y., Tian T., Jin G., Shu Y., Chen Y., Xu L., Zen K., Zhang C., Shen H.: Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol., 2010; 28: 1721-1726
  Google Scholar
• 20. Huang J., Wu J., Li Y., Li X., Yang T., Yang Q., Jiang Y.: Deregulation of serum microRNA expression is associated with cigarette smoking and lung cancer. Biomed. Res. Int., 2014; 2014: 364316
  Google Scholar
• 21. Jeong H.C., Kim E.K., Lee J.H., Lee J.M., Yoo H.N., Kim J.K.: Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients. Mol. Med. Rep., 2011; 4: 383-387
  Google Scholar
• 22. Jiang M., Zhang P., Hu G., Xiao Z., Xu F., Zhong T., Huang F., Kuang H., Zhang W.: Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients. Mol. Cell Biochem., 2013; 383: 67-75
  Google Scholar
• 23. Joerger M., Baty F., Früh M., Droege C., Stahel R.A., Betticher D.C., von Moos R., Oschsenbein A., Pless M., Gautschi O., Rothschild S., Brauchli P., Klingbiel D., Zappa F., Brutsche M.: Circulating microRNA profiling in patients with advanced non-squamous NSCLC receiving bevacizumab/erlotinib followed by platinum-based chemotherapy at progression (SAKK 19/05). Lung Cancer, 2014; 85: 306-313
  Google Scholar
• 24. Keller A., Leidinger P., Gislefoss R., Haugen A., Langseth H., Staehler P., Lenhof H.P., Meese E.: Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis. RNA Biol., 2011; 8: 506-516
  Google Scholar
• 25. Lawrie C.H., Gal S., Dunlop H.M., Pushkaran B., Liggins A.P., Pulford K., Banham A.H., Pezzella F., Boultwood J., Wainscoat J.S. Hatton C.S., Harris A.L.: Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol., 2008; 141: 672-675
  Google Scholar
• 26. Le H.B., Zhu W.Y., Chen D.D., He J.Y., Huang Y.Y., Liu X.G., Zhang Y.K.: Evaluation of dynamic change of serum miR-21 and miR-24 in pre – and post-operative lung carcinoma patients. Med. Oncol., 2012; 29: 3190-3197
  Google Scholar
• 27. Lee R.C., Feinbaum R.L., Ambros V.: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 1993; 75: 843-854
  Google Scholar
• 28. Leidinger P., Galata V., Backes C., Stähler C., Rheinheimer S., Huwer H., Meese E., Keller A.: Longitudinal study on circulating miRNAs in patients after lung cancer resection. Oncotarget, 2015; 6: 16674-16685
  Google Scholar
• 29. Lin P.Y., Yu S.L., Yang P.C.: MicroRNA in lung cancer. Br. J. Cancer, 2010; 103: 1144-1148
  Google Scholar
• 30. Lin Q., Mao W., Shu Y., Lin F., Liu S., Shen H., Gao W., Li S., Shen D.: A cluster of specified microRNAs in peripherial blood as biomarkers for metastatic non-small-cell lung cancer by stem-loop RT-PCR. J. Cancer. Res. Clin. Oncol., 2012; 138: 85-93
  Google Scholar
• 31. Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., Downing J.R., Jacks T., Horvitz H.R., Golub T.R.: MicroRNA expression profiles classify human cancers. Nature, 2005; 435: 834-838
  Google Scholar
• 32. Lytle J.R., Yario T.A., Steitz J.A.: Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5› UTR as in the 3› UTR. Proc. Natl. Acad. Sci. USA, 2007; 104: 9667-9672
  Google Scholar
• 33. Ma J., Li N., Guarnera M., Jiang F.: Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights, 2013; 8: 127-136
  Google Scholar
• 34. MacLellan S.A., MacAulay C., Lam S., Garnis C.: Pre-profiling factors influencing serum microRNA levels. BMC Clin. Pathol., 2014; 14: 27
  Google Scholar
• 35. Manser R., Lethaby A., Irving L.B., Stone C., Byrnes G., Abramson M.J., Campbell D.: Screening for lung cancer. Cochrane Database Syst. Rev., 2013; 6: CD001991
  Google Scholar
• 36. Mitchell P.S., Parkin R.K., Kroh E.M., Fritz B.R., Wyman S.K., Pogosova-Agadjanyan E.L., Peterson A., Noteboom J., O’Briant K.C., Allen A., Lin D.W., Urban N., Drescher C.W., Knudsen B.S., Stirewalt D.L. i wsp.: Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA, 2008; 105: 10513-10518
  Google Scholar
• 37. Mo D., Gu B., Gong X., Wu L., Wang H., Jiang Y., Zhang B., Zhang M., Zhang Y., Xu J., Pan S.: miR-1290 is a potential prognostic biomarker in non-small cell lung cancer. J. Thorac. Dis., 2015; 7: 1570-1579
  Google Scholar
• 38. Montani F., Marzi M.J., Dezi F., Dama E.,Carletti R.M., Bonizzi G., Bertolotti R., Bellomi M., Rampinelli C., Maisonneuve P., Spaggiari L., Veronesi G., Nicassio F., Di Fiore P.P., Bianchi F.: miR-Test: a blood test for lung cancer early detection. J. Natl. Cancer. Inst., 2015; 107: djv063
  Google Scholar
• 39. Mozzoni P., Banda I., Goldoni M., Corradi M., Tiseo M., Acampa O., Balestra V., Ampollini L., Casalini A., Carbognani P., Mutti A.: Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer. Biomarkers, 2013; 18: 679-686
  Google Scholar
• 40. Nowotwory płuca i opłucnej. http://onkologia.org.pl/nowotwory-pluca-oplucnej-tchawicy/(09.04.2016)
  Google Scholar
• 41. Patnaik S.K., Yendamuri S., Kannisto E., Kucharczuk J.C., Singhal S., Vachani A.: MicroRNA expression profiles of whole blood in lung adenocarcinoma. PLoS One, 2012; 7: e46045
  Google Scholar
• 42. Petriella D., De Summa S., Lacalamita R., Galetta D., Catino A., Logroscino A.F., Palumbo O., Carella M., Zito F.A., Simone G., Tommasi S.: miRNA profiling in serum and tissue samples to asses noninvasive biomarkers for NSCLC clinical outcome. Tumor Biol., 2016; 37: 5503-5513
  Google Scholar
• 43. Powrózek T., Krawczyk P., Kowalski D.M., Kuźnar-Kaminska B., Winiarczyk K., Olszyna-Serementa M., Batura-Gabryel H., Milanowski J.: Application of plasma circulating microRNA-448, 506, 4316, and 4478 analysis for non-invasive diagnosis of lung cancer. Tumor Biol., 2016; 37: 2049-2055
  Google Scholar
• 44. Powrózek T., Krawczyk P., Kowalski D.M., Winiarczyk K., Olszyna-Serementa M., Milanowski J.: Plasma circulating microRNA-944 and microRNA-3662 as potential histologic type-specific early lung cancer biomarkers. Transl. Res., 2015; 166: 315-323
  Google Scholar
• 45. Qi Z., Yang D.Y., Cao J.: Increased micro-RNA 17, 21, and 192 gene expressions improve early diagnosis in non-small cell lung cancer. Med. Oncol., 2014; 31: 195
  Google Scholar
• 46. Rabinowits G., Gercel-Taylor C., Day J.M., Taylor D.D., Kloecker G.H.: Exosomal microRNA: a diagnostic marker for lung cancer. Clin. Lung Cancer, 2009; 10: 42-46
  Google Scholar
• 47. Roa W.H., Kim J.O., Razzak R., Du H., Guo L., Singh R., Gazala S., Ghosh S., Wong E., Joy A.A, Xing J.Z., Bedard E.L.: Sputum microRNA profiling: a novel approach for the early detection of non-small cell lung cancer. Clin. Invest. Med., 2012; 35: E271-E281
  Google Scholar
• 48. Rossi G., Pelosi G., Barbareschi M., Graziano P., Cavazza A., Papotti M.: Subtyping non-small cell lung cancer: relevant issues and operative recommendations for the best pathology practice. Int. J. Surg. Pathol., 2013; 21: 326-336
  Google Scholar
• 49. Roth C., Stückrath I., Pantel K., Izbicki J.R., Tachezy M., Schwarzenbach H.: Low levels of cell-free circulating miR-361-3p and miR- 625* as blood-based markers for discriminating malignant from benign lung tumors. PLoS One, 2012; 7: e38248
  Google Scholar
• 50. Shen J., Liao J., Guarnera M.A., Fang H., Cai L., Stass S.A., Jiang F.: Analysis of microRNAs in sputum to improve computed tomography for lung cancer diagnosis. J. Thorac. Oncol., 2014; 9: 33-40
  Google Scholar
• 51. Shen J., Todd N.W., Zhang H., Yu L., Lingxiao X., Mei Y., Guarnera M., Liao J., Chou A., Lu C.L., Jiang Z., Fang H., Katz R.L., Jiang F.: Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab. Invest., 2011; 91: 579-587
  Google Scholar
• 52. Shen Y., Tang D., Yao R., Wang M., Wang Y., Yao Y., Li X., Zhang H.: microRNA expression profiles associated with survival, disease progression, and response to gefitinib in completely resected non-small-cell lung cancer with EGFR mutation. Med. Oncol., 2013; 30: 750
  Google Scholar
• 53. Shi S.B., Wang M., Tian J., Li R., Chang C.X., Qi J.L.: MicroRNA 25, microRNA 145, and microRNA 210 as biomarkers for predicting the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who are negative for epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations. Transl. Res., 2016; 170: 1-7
  Google Scholar
• 54. ilva J., Garcia V., Zaballos A., Provencio M., Lombardia L., Almonacid L., Garcia J.M., Dominguez G., Peña C., Diaz R., Herrera M., Varela A., Bonilla F.: Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. Eur. Respir. J., 2011; 37: 617-623
  Google Scholar
• 55. Tang D., Shen Y., Wang M., Yang R., Wang Z., Sui A, Jiao W., Wang Y.: Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur. J. Cancer Prev., 2013; 22: 540-548
  Google Scholar
• 56. Turchinovich A., Samatov T.R., Tonevitsky A.G., Burwinkel B.: Circulating miRNAs: cell-cell communication function? Front. Genet., 2013; 4: 119
  Google Scholar
• 57. Turchinovich A., Weiz L., Langheinz A., Burwinkel B.: Characterization of extracellular circulating microRNA. Nucleic Acids Res., 2011; 39: 7223-7233
  Google Scholar
• 58. Ulivi P., Foschi G., Mengozzi M., Scarpi E., Silvestrini R., Amadori D., Zoli W.: Peripherial blood miR-328 expression as a potential biomarker for the early diagnosis of NSCLC. Int. J. Mol. Sci., 2013; 14: 10332-10342
  Google Scholar
• 59. Valadi H., Ekström K., Bossios A., Sjöstrand M., Lee J.J., Lötvall J.O.: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007; 9: 654-659
  Google Scholar
• 60. Vickers K.C., Palmisano B.T., Shoucri B.M., Shamburek R.D., Remaley A.T.: MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol., 2011; 13: 423-433
  Google Scholar
• 61. Wang Q., Zhong M., Liu W., Li J., Huang J., Zheng L.: Alterations of microRNAs in cisplatin-resistant human non-small cell lung cancer cells (A549/DDP). Exp. Lung. Res., 2011; 37: 427-434
  Google Scholar
• 62. Wang R.J., Zheng Y.H., Wang P., Zhang J.Z.: Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer. Int. J. Clin. Exp. Pathol., 2015; 8: 765-771
  Google Scholar
• 63. Wang Y., Gu J., Roth J.A., Hildebrandt M.A., Lippman S.M., Ye Y., Minna J.D., Wu X.: Pathway-based serum microRNA profiling and survival in patients with advanced stage non-small cell lung cancer. Cancer Res., 2013; 73: 4801-4809
  Google Scholar
• 64. Weber J.A., Baxter D.H., Zhang S., Huang D.Y., Huang K.H., Lee M.J., Galas D.J., Wang K.: The microRNA spectrum in 12 body fluids. Clin. Chem., 2010; 56: 1733-1741
  Google Scholar
• 65. Wei J., Gao W., Zhu C.J., Liu Y.Q., Mei Z., Cheng T., Shu Y.Q.: Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer. Chin. J. Cancer, 2011; 30: 407-414
  Google Scholar
• 66. Wightman B., Ha I., Ruvkun G.: Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 1993; 75: 855-862
  Google Scholar
• 67. Yang J.S., Li B.J., Lu H.W., Chen Y., Lu C., Zhu R.X., Liu S.H., Yi Q.T., Li J., Song C.H.: Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening. Tumor Biol., 2015; 36: 3035-3042
  Google Scholar
• 68. Yu L., Todd N.W., Xing L., Xie Y., Zhang H., Liu Z., Fang H., Zhang J., Katz R.L., Jiang F.: Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int. J. Cancer, 2010; 127: 2870-2878
  Google Scholar
• 69. Yuxia M., Zhennan T., Wei Z.: Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis. J. Cancer Res. Clin. Oncol., 2012; 138: 2045-2050
  Google Scholar
• 70. Zampetaki A., Willeit P., Drozdov I., Kiechl S., Mayr M.: Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc. Res., 2012; 93: 555-562
  Google Scholar
• 71. Zen K., Zhang C.Y.: Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med. Res. Rev., 2012; 32: 326-348
  Google Scholar
• 72. Zhao Q., Cao J., Wu Y.C., Liu X., Han J., Huang X.C., Jiang L.H., Hou X.X., Mao W.M., Ling Z.Q.: Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers. Am. J. Cancer Res., 2015; 5: 1692-1705
  Google Scholar
• 73. Zhao W., Zhao J.J., Zhang L., Xu Q.F., Zhao Y.M., Shi X.Y., Xu A.G.: Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer. Int. J. Clin. Exp. Med., 2015; 8: 14759-14763
  Google Scholar
• 74. Zheng D., Haddadin S., Wang Y., Gu L.Q., Perry M.C., Freter C.E., Wang M.X.: Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int. J. Clin. Exp. Pathol., 2011; 4: 575-586
  Google Scholar
• 75. Zhu W., He J., Chen D., Zhang B., Xu L., Ma H., Liu X., Zhang Y., Le H.: Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS One, 2014; 9: e87780
  Google Scholar

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