Basic & Clinical Cancer Research 2017. 9(4):13-21.

The Evaluation of miR-21 Level in Lung Tissue and Plasma of Nsclc Patients
Ayda Arab, Morteza Karimipoor, Shiva Irani, Arda Kiani, Sirous Zeinali, Elham Tafsiri, Kambiz Sheikhy


Background: Lung cancer is one of the most common malignant tumors with poor survival, which is usually diagnosed at advanced stages. In recent years, increasing evidence has revealed that circulating miRNAs exhibit great potential in screening and early detection of various types of cancers including lung cancer. miR-21 is one of the most highly expressed members of the microRNA family in many human cancer types.
Methods: The authors analyzed miR-21 expression in matched tumor and normal tissues and plasma in 17 patients affected with non-small cell lung cancer. Samples were collected from the NSCLC patients before surgery, radiotherapy or chemotherapy. Expression levels of tissue miR-21 were assessed, using TaqMan RT-PCR assay. Expression levels of plasma miR-21 were assessed, using LNA™ RT microRNA PCR primer set and SYBR green qRT-PCR assay.
Results: miR-21 expression was higher in 9 out of 17 patients’ plasma samples. No change in miR-21 expression was observed in 8 plasma samples. In lung tissues, ten patients showed up-regulation of miR-21 and six patients were down-regulated. One patient had no change in miR-21 expression level in tissue samples. The expression level of mir-21 in tissue and plasma was concordant in 6 patients.
Conclusion: It seems that the level of miR-21 in plasma samples of NSCLC patients as a marker for screening needs more investigation.


Non-small cell lung cancer; miR-21; plasma; tissue

Full Text:



Almasi Z, Salehiniya H, Amoori N, Enayatrad M. Epidemi¬ology characteristics and trends of lung cancer incidence in Iran. Asian Pac J Cancer Prev. 2016;17:557-62.

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA: a cancer journal for clinicians. 2012;62(4):220-41.

Team NLSTR. Reduced lung-cancer mortality with low-dose computed tomographic screening. NEngl J Med 2011;365:395–409.

Arab A, Karimipoor M, Irani S, Kiani A, Zeinali S, Tafsiri E, et al. Potential circulating miRNA signature for early de¬tection of NSCLC. Cancer Genetics 2017;216:150-8.

Sassen S, Miska EA, Caldas C. MicroRNA—implications for cancer. Virchows Archiv. 2008;452(1):1-10.6

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in can¬cers. Proceedings of the National academy of Sciences of the United States of America. 2004;101:2999-3004.

Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33(20):e179.

Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, Degli Uberti EC. miR-15a and miR-16-1 down-regulation in pitui¬tary adenomas. J Cell Physiol. 2005;204:280-5.

Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sab¬bioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005;65:7065-70.

Jazdzewski K, Murray E, Franssila K, Jarząb B, Schoenberg D, Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 2008;105:7269-74.

Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and ad¬hesion-independent growth. Cancer Res. 2007;67:8433-8.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human can¬cers. Nature 2005;435:834-8.

Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006;9:189-98.

Lui W-O, Pourmand N, Patterson BK, Fire A. Patterns of known and novel small RNAs in human cervical cancer. Cancer Res. 2007;67:6031-43.

Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casa¬lini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699-707.

Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, et al. Expression profiling identifies microRNA signa¬ture in pancreatic cancer. Int J Cancer. 2007;120:1046-54.

Szafranska A, Davison T, John J, Cannon T, Sipos B, Magh¬nouj A, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancre¬atic ductal adenocarcinoma. Oncogene. 2007;26:4442-52.

Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, et al. MicroRNA expression patterns to differen¬tiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297:1901-8.

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, PogosovaAgadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008;105:10513-8.

Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of bio¬markers for diagnosis of cancer and other diseases. Cell Res 2008;18:997-1006.

Wong T-S, Liu X-B, Wong BY-H, Ng RW-M, Yuen AP-W, Wei WI. Mature miR-184 as Potential oncogenic microR¬NA of squamous cell carcinoma of tongue. Clin Cancer Res 2008;14:2588-92.

Ng EK, Chong WW, Lam EK, Shin VY, Yu J, Poon TC, et al. Differential expression of microRNAs in plasma of colorectal cancer patients: A potential marker for colorectal cancer screening. Gut 2009;58:1375-81.

Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of pa¬tients with gastric cancers. Br J Cancer 2010;102:1174-79.

Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 2010;16:360-4.

Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le Q-T, et al. Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Transl Oncol. 2010;3:109-13.

Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 2011;108:5003- 8.

Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and de¬livered to recipient cells by high-density lipoproteins. Nat Cell Biol 2011;13:423-33.

Hasselmann DO, Rappl G, Tilgen W, Reinhold U. Ex¬tracellular tyrosinase mRNA within apoptotic bodies is protected from degradation in human serum. Clin Chem 2001;47:1488-9.

Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends in cell biology. 2009;19:43- 1.

Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010;285:17442-52.

Li B, Ren S, Li X, Wang Y, Garfield D, Zhou S, et al. MiR- 21 overexpression is associated with ac¬quired resistance of EGFR-TKI in non-small cell lung cancer. Lung Cancer 2014;83:146-53.

Wagenaar TR, Zabludoff S, Ahn S-M, Allerson C, Arlt H, Baffa R, et al. Anti-miR-21 sup¬presses hepatocellular carcinoma growth via broad transcriptional network deregula¬tion. Mol Cancer Res 2015;13:1009-21.

Nouraee N, Van Roosbroeck K, Vasei M, Semnani S, Samaei NM, Naghshvar F, et al. Expression, tissue distribution and function of miR-21 in esopha¬geal squamous cell carcinoma. PLoS One 2013;8: e73009.

Esquela-Kerscher A, Slack FJ. OncomirsmicroRNAs with a role in cancer. Nat Rev Cancer 2006;6:259-69.

Tafsiri E, Darbouy M, Shadmehr MB, Zagryazhskaya A, Alizadeh J, Karimipoor M. Expression of miRNAs in non-small-cell lung carcinomas and their association with clinico¬pathological features. Tumor Biology. 2015;36(3):1603-12.

Chen Y, Chen J, Wang H, Shi J, Wu K, Liu S, et al. HCV-in¬duced miR-21 contributes to evasion of hostimmune sys¬tem by targeting MyD88 and IRAK1. PLoSPathog. (2013) 9:e1003248.

Goldstraw P, Crowley J, Chansky K. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706–14.

Koturbash I, Zemp FJ, Pogribny I, Kovalchuk O. Small molecules with big effects: the role of the microRNAome in cancer and carcinogenesis. Mutation Research—Genetic Toxicology and EnvironmentalMutagenesis. 2011;722, no. 2:94–105.

Tang D, Shen Y, Wang M, Yang R, Wang Z, Sui A, et al. Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur J Cancer Prev 2013;22:540-54.

Yin C, Zhou X, Dang Y, Yan J, Zhang G. Potential role of circulating MiR-21 in the diagnosis and prognosis of diges¬tive system cancer: a systematic review and meta-analysis. Medicine. 2015;94(50).

Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol (2009) 182:4994–5002.

Sonkoly E, Wei T, Janson PC, Sääf A, Lundeberg L, TengvallLinder M, et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One (2007) 2:e610.

Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A, Petroc¬ca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc NatlAcadSciUSA 2006;103:2257–61.

Cameron JE, Fewell C, Yin Q, McBride J, Wang X, Lin Z, et al. Epstein-Barr virus growth/latency III program alters cellular microRNA expression. Virology. (2008) 382:257–66.

Huang J, Ma G, Fu L, Jia H, Zhu M, Li X, et al. Pseudora¬bies viral replication is inhibited by a novel target of miR- 21. Virology. (2014) 45:(6–457)319–28.

LiuPT, WheelwrightM, TelesR, KomisopoulouE, EdfeldtK, FergusonB. MicroRNA-21 targets the vitamin d-dependent antimicrobial pathway in lep- rosy. NatMed (2012) 18:267–73.

Qiu X, Dong S, Qiao F, Lu S, Song Y, Lao Y, et al. HBx-me¬diated miR-21 upreg- ulation represses tumor-suppressor function of PDCD4 in hepatocellular carcinoma. Oncogene (2013) 32:3296–305.

Wu Z, Lu H, Sheng J, Li L. Inductive microRNA-21 impairs antimycobacterial responses by targeting IL-12 and Bcl-2. FEBS Lett. (2012);586:2459–67.

Shi C, Liang Y, Yang J, Xia Y, Chen H, Han H. MicroR¬NA-21 knock- out improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tis¬sue injury. PLoSOne. (2013);8:e66814.

Raitoharju E, Lyytikäinen L-P, Levula M, Oksala N, Mennander A, Tarkka M, et al. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study. Atherosclerosis. 2011;219(1):211-7.

Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, et al. Identification of novel microRNA signatures linked to human lupus disease activity and patho¬genesis: miR-21 regulates aberrant Tcell responses through regulation of PDCD4 expression. AnnRheumDis. (2011) 70:1496–506.

Samadaian N, Modaresi MH, Mobasheri M, Ebrahim Zadeh Vesal R, Akrami SM. miRNA-21 expression analysis in 35 colorectal cancer. Tehran University Medical Journal TUMS Publications. 2014;72(5):301-6.

Solomides CC, Evans BJ, Navenot J-M, Vadigepalli R, Peiper SC, Wang Z-x. MicroRNA profiling in lung cancer reveals new molecular markers for diagnosis. Acta cytolog¬ica. 2012;56(6):645-54.

Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC. Circulating micro-RNA expression pro¬files in early stage nonsmall cell lung cancer. Int J Cancer 2012;130:1378-86.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.