| Note | |
| | |
| Entity | Breast cancer |
| Prognosis | mir-146b-5p along with other microRNAs may permit to differentiate breast tumour sub-types. However, conflicting results have been obtained. One study, where miR-146b has been analysed in 167 breast cancer cases, showed an elevated expression in triple negative breast tumours. This study comprised analyses of several different tumour mammary cell lines and miR-146b-5p was found to be the most expressed in basal-like tumour cell lines (Garcia et al., 2011).
A second study, based on 20 samples only, identified specific expression of a set of seven microRNAs (including miR-146b-5p) in normal basal cells but not in basal-like breast cancers, which are close to triple negative breast cancers. miR-146b-5p may have an elevated expression in malignant myoepithelioma of the breast (Bockmeyer et al., 2011). |
| Oncogenesis | Two studies described a biological role for miR-146b in breast tumour progression. The BRMS1 (Breast cancer Metastasis Suppressor 1) protein up-regulated the expression of miR-146b in MDA-MB-435, a tumour mammary cell line. Moreover, the overexpression of this microRNA down-regulated the expression of EGFR (Epidermal Growth Factor Receptor) in another tumour cell line, MDA-MB-231. This study showed an impact, in vitro, of miR-146b on invasion and migration of cells and on the suppression of metastasis (Bockmeyer et al., 2011).
The second study depicted a direct target of miR-146b-5p, BRCA1 (BReast CAncer 1), one of the two major breast cancer predisposition genes. The binding of miR-146-5p to the BRCA1 3'UTR decreased the expression of BRCA1, induced cellular proliferation and reduced the homologous recombination rate. miR-146b seemed to have an important role in tumour progression via BRCA1 (Garcia et al., 2011). |
| | |
| | |
| Entity | Thyroid cancer |
| Disease | Three studies showed that miR-146b, along with a set of other microRNAs, are overexpressed in tumours versus hyperplasic nodules or versus uncertain malignant potential tumours (Nikiforova et al., 2008; Lassalle et al., 2011; Chen et al., 2008). miR-146b is consistently overexpressed in both papillary and follicular thyroid carcinomas (Chen et al., 2008) and is associated with extrathyroidal invasion (Chou et al., 2010) and with aggressive papillary thyroid carcinoma (Yip et al., 2011). Of note, in these two studies, miR-146b overexpression seems correlated with BRAF mutations. |
| Prognosis | The expression of miR-146b and of a set of six other microRNAs was able to predict malignancy of thyroid fine needle aspiration specimens (Shen et al., 2012; Agretti et al., 2012). |
| Oncogenesis | In thyroid follicular cells, miR-146b-5p was shown to bind directly the 3'UTR of SMAD4, an important member of the TGF-β signalling pathway. This modulation of the TGF-β signal confirmed the oncogenic role of miR-146b-5p in thyroid cancers (Geraldo et al., 2012). |
| | |
| | |
| Entity | Lung cancer |
| Prognosis | A microarray analysis of 61 squamous cell carcinoma samples versus 10 normal lung samples showed that miR-146b had the strongest prediction accuracy for stratifying Non-Small Cell Lung Cancer (NSCLC) in prognostic groups (Raponi et al., 2009). Another study completed this observation and found a significant reduction of a set of seven microRNAs (including miR-146b) in serum of NSCLC patients (Heegaard et al., 2012). |
| Oncogenesis | A study analysed the effect of miR-146b overexpression in A549 lung cancer cells. A 3-8-fold increase in the expression of pre-miR-146b did not alter the major cellular functions classically involved in oncogenesis, such as proliferation, migration or invasiveness. This overexpression only impacted the ability to form colonies, perhaps because miR-146b-5p and miR-146b-3p may have opposing effects (Patnaik et al., 2011). |
| | |
| | |
| Entity | Other cancers |
| Note | (like prostate, pancreas, kidney, colorectal) |
| Disease | microRNA profiling by microarrays has shown that miR-146b is overexpressed in many cancer types, such as glioma (Xia et al., 2009), melanoma (Jukic et al., 2010), oesophageal cancer (Zhao et al., 2012), bladder cancer (Pignot et al., 2012), colorectal cancer (Ragusa et al., 2010) or oral cancers (Scapoli et al., 2010). miR-146b seems to be also overexpressed in some prostate and colorectal cancers (Kanaan et al., 2012). |
| | |
| | |
| Entity | Immunity |
| Note | Innate immunity and inflammation play an important role in cancer development and it is therefore noteworthy to mention that the miR-146 family is involved in these mechanisms of cell protection. Even if more evidence has been gathered in the case of the former, both miR-146a and miR-146b control Toll-like receptor and cytokine signaling pathways. miR-146b is predicted to bind the 3'UTR of the IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6 transcripts. The expression of MIR146B is regulated by NF-κB (Taganov et al., 2006). |
| | |
| MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration. |
| Agretti P, Ferrarini E, Rago T, Candelieri A, De Marco G, Dimida A, Niccolai F, Molinaro A, Di Coscio G, Pinchera A, Vitti P, Tonacchera M. |
| Eur J Endocrinol. 2012 Sep;167(3):393-400. doi: 10.1530/EJE-12-0400. Epub 2012 Jun 22. |
| PMID 22728346 |
| |
| MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes. |
| Bockmeyer CL, Christgen M, Muller M, Fischer S, Ahrens P, Langer F, Kreipe H, Lehmann U. |
| Breast Cancer Res Treat. 2011 Dec;130(3):735-45. doi: 10.1007/s10549-010-1303-3. Epub 2011 Mar 17. |
| PMID 21409395 |
| |
| MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. |
| Chen YT, Kitabayashi N, Zhou XK, Fahey TJ 3rd, Scognamiglio T. |
| Mod Pathol. 2008 Sep;21(9):1139-46. doi: 10.1038/modpathol.2008.105. Epub 2008 Jun 27. |
| PMID 18587330 |
| |
| miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. |
| Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC, Liu RT. |
| Thyroid. 2010 May;20(5):489-94. doi: 10.1089/thy.2009.0027. |
| PMID 20406109 |
| |
| Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. |
| Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaelian I, Mazoyer S. |
| EMBO Mol Med. 2011 May;3(5):279-90. doi: 10.1002/emmm.201100136. Epub 2011 Apr 5. |
| PMID 21472990 |
| |
| MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer. |
| Geraldo MV, Yamashita AS, Kimura ET. |
| Oncogene. 2012 Apr 12;31(15):1910-22. doi: 10.1038/onc.2011.381. Epub 2011 Aug 29. |
| PMID 21874046 |
| |
| Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. |
| Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC. |
| Int J Cancer. 2012 Mar 15;130(6):1378-86. doi: 10.1002/ijc.26153. Epub 2011 Aug 26. |
| PMID 21544802 |
| |
| Microrna profiling analysis of differences between the melanoma of young adults and older adults. |
| Jukic DM, Rao UN, Kelly L, Skaf JS, Drogowski LM, Kirkwood JM, Panelli MC. |
| J Transl Med. 2010 Mar 19;8:27. doi: 10.1186/1479-5876-8-27. |
| PMID 20302635 |
| |
| Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer. |
| Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C, Cohen E, Roberts H, Keskey B, Petras RE, Crawford NP, Galandiuk S. |
| Hum Mutat. 2012 Mar;33(3):551-60. doi: 10.1002/humu.22021. |
| PMID 22241525 |
| |
| Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland? |
| Lassalle S, Hofman V, Ilie M, Bonnetaud C, Puissegur MP, Brest P, Loubatier C, Guevara N, Bordone O, Cardinaud B, Lebrigand K, Rios G, Santini J, Franc B, Mari B, Al Ghuzlan A, Vielh P, Barbry P, Hofman P. |
| Endocr Relat Cancer. 2011 Sep 13;18(5):579-94. doi: 10.1530/ERC-10-0283. Print 2011 Oct. |
| PMID 21778212 |
| |
| MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. |
| Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. |
| J Clin Endocrinol Metab. 2008 May;93(5):1600-8. doi: 10.1210/jc.2007-2696. Epub 2008 Feb 12. |
| PMID 18270258 |
| |
| Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells. |
| Patnaik SK, Kannisto E, Mallick R, Yendamuri S. |
| PLoS One. 2011;6(7):e22379. doi: 10.1371/journal.pone.0022379. Epub 2011 Jul 18. |
| PMID 21789255 |
| |
| Microrna expression profile in a large series of bladder tumors: Identification of a 3-mirna signature associated with aggressiveness of muscle-invasive bladder cancer. |
| Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, Zerbib M, Lidereau R, Debre B, Amsellem-Ouazana D, Bieche I. |
| Int J Cancer. 2012 Nov 20. doi: 10.1002/ijc.27949. [Epub ahead of print] |
| PMID 23169479 |
| |
| Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment. |
| Ragusa M, Majorana A, Statello L, Maugeri M, Salito L, Barbagallo D, Guglielmino MR, Duro LR, Angelica R, Caltabiano R, Biondi A, Di Vita M, Privitera G, Scalia M, Cappellani A, Vasquez E, Lanzafame S, Basile F, Di Pietro C, Purrello M. |
| Mol Cancer Ther. 2010 Dec;9(12):3396-409. doi: 10.1158/1535-7163.MCT-10-0137. Epub 2010 Sep 29. |
| PMID 20881268 |
| |
| MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. |
| Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG. |
| Cancer Res. 2009 Jul 15;69(14):5776-83. doi: 10.1158/0008-5472.CAN-09-0587. Epub 2009 Jul 7. |
| PMID 19584273 |
| |
| MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. |
| Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A, Farinella F, Mazzotta M, Carinci F. |
| Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1229-34. |
| PMID 21244772 |
| |
| MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases. |
| Shen R, Liyanarachchi S, Li W, Wakely PE Jr, Saji M, Huang J, Nagy R, Farrell T, Ringel MD, de la Chapelle A, Kloos RT, He H. |
| Thyroid. 2012 Jan;22(1):9-16. doi: 10.1089/thy.2011.0081. Epub 2011 Dec 2. |
| PMID 22136206 |
| |
| NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. |
| Taganov KD, Boldin MP, Chang KJ, Baltimore D. |
| Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12481-6. Epub 2006 Aug 2. |
| PMID 16885212 |
| |
| microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. |
| Xia H, Qi Y, Ng SS, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, Chen Y, He ML, Kung HF, Lai L, Lin MC. |
| Brain Res. 2009 May 7;1269:158-65. doi: 10.1016/j.brainres.2009.02.037. Epub 2009 Mar 3. |
| PMID 19265686 |
| |
| MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. |
| Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, Nikiforova MN. |
| Ann Surg Oncol. 2011 Jul;18(7):2035-41. doi: 10.1245/s10434-011-1733-0. Epub 2011 May 3. |
| PMID 21537871 |
| |
| microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma. |
| Zhao Y, Schetter AJ, Yang GB, Nguyen G, Mathe EA, Li P, Cai H, Yu L, Liu F, Hang D, Yang H, Wang XW, Ke Y, Harris CC. |
| Int J Cancer. 2012 Nov 23. doi: 10.1002/ijc.27954. [Epub ahead of print] |
| PMID 23175214 |
| |
