Crosstalk Between Kinases, Phosphatases And Mirnas In Cancer

Reversible phosphorylation of proteins, performed by kinases and phosphatases, is the major post translational protein modification in eukaryotic cells. This intracellular event represents a critical regulatory mechanism of several signaling pathways and can be related to a vast array of diseases, including cancer. Cancer research has produced increasing evidence that kinase and phosphatase activity can be compromised by mutations and also by miRNA silencing, performed by small non-coding and endogenously produced RNA molecules that lead to translational repression. miRNAs are believed to target about one-third of human mRNAs while a single miRNA may target about 200 transcripts simultaneously. Regulation of the phosphorylation balance by miRNAs has been a topic of intense research over the last years, spanning topics going as far as cancer aggressiveness and chemotherapy resistance. By addressing recent studies that have shown miRNA expression patterns as phenotypic signatures of cancers and how miRNA influence cellular processes such as apoptosis, cell cycle control, angiogenesis, inflammation and DNA repair, we discuss how kinases, phosphatases and miRNAs cooperatively act in cancer biology.107PB167187Hunter, T., Cooper, J.A., Protein-tyrosine kinases (1985) Annu. Rev. Biochem., 54, pp. 897-930Graves, J.D., Krebs, E.G., Protein phosphorylation and signal transduction (1999) Pharmacol. Ther., 82, pp. 111-121Manning, G., Whyte, D.B., Martinez, R., Hunter, T., Sudarsanam, S., The protein kinase complement of the human genome (2002) Science, 298, pp. 1912-1934Manning, G., Plowman, G.D., Hunter, T., Sudarsanam, S., Evolution of protein kinase signaling from yeast to man (2002) Trends Biochem. Sci., 27, pp. 514-520Gee, C.E., Mansuy, I.M., Protein phosphatases and their potential implications in neuroprotective processes (2005) Cell. Mol. Life Sci. CMLS, 62, pp. 1120-1130Tonks, N.K., Protein tyrosine phosphatases: From genes, to function, to disease (2006) Nat. Rev. Mol. Cell Biol., 7, pp. 833-846Easty, D., Gallagher, W., Bennett, D.C., Protein tyrosine phosphatases, new targets for cancer therapy (2006) Curr. Cancer Drug Targets, 6, pp. 519-532Caenepeel, S., Charydczak, G., Sudarsanam, S., Hunter, T., Manning, G., The mouse kinome: Discovery and comparative genomics of all mouse protein kinases (2004) Proc. Natl. Acad. Sci. U. S. A., 101, pp. 11707-11712Zhu, H., Klemic, J.F., Chang, S., Bertone, P., Casamayor, A., Klemic, K.G., Analysis of yeast protein kinases using protein chips (2000) Nat. Genet., 26, pp. 283-289Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Friedberg, I., Osterman, A., Protein tyrosine phosphatases in the human genome (2004) Cell, 117, pp. 699-711Shi, Y., Serine/threonine phosphatases: Mechanism through structure (2009) Cell, 139, pp. 468-484Reagan-Shaw, S., Ahmad, N., Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: Implications for the treatment of prostate cancer (2005) FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 19, pp. 611-613Steegmaier, M., Hoffmann, M., Baum, A., Lénárt, P., Petronczki, M., Krssák, M., BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo (2007) Curr. Biol. CB, 17, pp. 316-322Tandle, A.T., Kramp, T., Kil, W.J., Halthore, A., Gehlhaus, K., Shankavaram, U., Inhibition of polo-like kinase 1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitisation (2013) Eur. J. Cancer Oxf. Engl., 1990 (49), pp. 3020-3028Biagioni, F., Bossel Ben-Moshe, N., Fontemaggi, G., Canu, V., Mori, F., Antoniani, B., MiR-10b∗, a master inhibitor of the cell cycle, is down-regulated in human breast tumours (2012) EMBO Mol. Med., 4, pp. 1214-1229Shi, W., Alajez, N.M., Bastianutto, C., Hui, A.B.Y., Mocanu, J.D., Ito, E., Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer (2010) Int. J. Cancer, 126, pp. 2036-2048Liu, J., Lu, K.-H., Liu, Z.-L., Sun, M., De, W., Wang, Z.-X., MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1 (2012) BMC Cancer, 12, p. 519Ito, T., Sato, F., Kan, T., Cheng, Y., David, S., Agarwal, R., Polo-like kinase 1 regulates cell proliferation and is targeted by miR-593∗ in esophageal cancer (2011) Int. J. Cancer, 129, pp. 2134-2146McGowan, C.H., Russell, P., Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15 (1993) EMBO J., 12, pp. 75-85Mahajan, K., Fang, B., Koomen, J.M., Mahajan, N.P., H2B Tyr37 phosphorylation suppresses expression of replication-dependent core histone genes (2012) Nat. Struct. Mol. Biol., 19, pp. 930-937Butz, H., Likó, I., Czirják, S., Igaz, P., Khan, M.M., Zivkovic, V., Down-regulation of Wee1 kinase by a specific subset of microRNA in human sporadic pituitary adenomas (2010) J. Clin. Endocrinol. Metab., 95, pp. 181-E191Esteller, M., Non-coding RNAs in human disease (2011) Nat. Rev. Genet., 12, pp. 861-874Creevey, L., Ryan, J., Harvey, H., Bray, I.M., Meehan, M., Khan, A.R., MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1 (2013) Mol. Cancer, 12, p. 23Li, D., Zhao, Y., Liu, C., Chen, X., Qi, Y., Jiang, Y., Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer (2011) Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res., 17, pp. 1722-1730Guo, S.T., Jiang, C.C., Wang, G.P., Li, Y.P., Wang, C.Y., Guo, X.Y., MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer (2013) Oncogene, 32, pp. 1910-1920Ng, W.L., Yan, D., Zhang, X., Mo, Y.-Y., Wang, Y., Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J (2010) DNA Repair, 9, pp. 1170-1175Yan, D., Ng, W.L., Zhang, X., Wang, P., Zhang, Z., Mo, Y.-Y., Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation (2010) PloS One, 5, p. 11397Hu, H., Du, L., Nagabayashi, G., Seeger, R.C., Gatti, R.A., ATM is down-regulated by N-Myc-regulated microRNA-421 (2010) Proc. Natl. Acad. Sci. U. S. A., 107, pp. 1506-1511Wang, J., He, J., Su, F., Ding, N., Hu, W., Yao, B., Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition (2013) Cell Death Dis., 4, p. 699Zhao, B., Li, L., Lei, Q., Guan, K.-L., The Hippo-YAP pathway in organ size control and tumorigenesis: An updated version (2010) Genes Dev., 24, pp. 862-874Harvey, K.F., Zhang, X., Thomas, D.M., The Hippo pathway and human cancer (2013) Nat. Rev. Cancer, 13, pp. 246-257Qin, W., Dong, P., Ma, C., Mitchelson, K., Deng, T., Zhang, L., MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways (2012) Oncogene, 31, pp. 4067-4075Rom, U.A., Nielsen, F.C., Lund, A.H., MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation (2008) Mol. Cell, 30, pp. 460-471Li, Y., Pei, J., Xia, H., Ke, H., Wang, H., Tao, W., Lats2, a putative tumor suppressor, inhibits G1/S transition (2003) Oncogene, 22, pp. 4398-4405Ke, H., Pei, J., Ni, Z., Xia, H., Qi, H., Woods, T., Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L) (2004) Exp. Cell Res., 298, pp. 329-338Tschöp, K., Conery, A.R., Litovchick, L., Decaprio, J.A., Settleman, J., Harlow, E., A kinase shRNA screen links LATS2 and the pRB tumor suppressor (2011) Genes Dev., 25, pp. 814-830Jiménez-Velasco, A., Román-Gómez, J., Agirre, X., Barrios, M., Navarro, G., Vázquez, I., Downregulation of the large tumor suppressor 2 (LATS2/KPM) gene is associated with poor prognosis in acute lymphoblastic leukemia (2005) Leukemia, 19, pp. 2347-2350Takahashi, Y., Miyoshi, Y., Takahata, C., Irahara, N., Taguchi, T., Tamaki, Y., Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers (2005) Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res., 11, pp. 1380-1385Jiang, Z., Li, X., Hu, J., Zhou, W., Jiang, Y., Li, G., Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma (2006) Neurosci. Res., 56, pp. 450-458Liu, X., Sempere, L.F., Ouyang, H., Memoli, V.A., Andrew, A.S., Luo, Y., MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors (2010) J. Clin. Invest., 120, pp. 1298-1309Voorhoeve, P.M., Le Sage, C., Schrier, M., Gillis, A.J.M., Stoop, H., Nagel, R., A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors (2006) Cell, 124, pp. 1169-1181Cho, W.J., Shin, J.M., Kim, J.S., Lee, M.R., Hong, K.S., Lee, J.-H., MiR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2 (2009) Mol. Cells, 28, pp. 521-527Lee, K.-H., Goan, Y.-G., Hsiao, M., Lee, C.-H., Jian, S.-H., Lin, J.-T., MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer (2009) Exp. Cell Res., 315, pp. 2529-2538Bartel, D.P., MicroRNAs: Genomics, biogenesis, mechanism, and function (2004) Cell, 116, pp. 281-297Bueno, M.J., Pérez De Castro, I., Gómez De Cedrón, M., Santos, J., Calin, G.A., Cigudosa, J.C., Genetic and epigenetic silencing of MicroRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression (2008) Cancer Cell, 13, pp. 496-506Li, Y., Wang, H., Tao, K., Xiao, Q., Huang, Z., Zhong, L., MiR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein (2013) Exp. Cell Res., 319, pp. 1094-1101Liu, Y., Song, Y., Ma, W., Zheng, W., Yin, H., Decreased microRNA-30a levels are associated with enhanced ABL1 and BCR-ABL1 expression in chronic myeloid leukemia (2013) Leuk. Res., 37, pp. 349-356Duquesnes, N., Lezoualc'H, F., Crozatier, B., PKC-delta and PKC-epsilon: Foes of the same family or strangers? (2011) J. Mol. Cell. Cardiol., 51, pp. 665-673Körner, C., Keklikoglou, I., Bender, C., Wörner, A., Münstermann, E., Wiemann, S., MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKCepsilon) (2013) J. Biol. Chem., 288, pp. 8750-8761Carnero, A., The PKB/AKT pathway in cancer (2010) Curr. Pharm. Des., 16, pp. 34-44Nicholson, K.M., Anderson, N.G., The protein kinase B/Akt signalling pathway in human malignancy (2002) Cell Signal., 14, pp. 381-395Cai, N., Wang, Y.-D., Zheng, P.-S., The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1 (2013) RNA N. Y., 19, pp. 85-95Tao, Z.-H., Wan, J.-L., Zeng, L.-Y., Xie, L., Sun, H.-C., Qin, L.-X., MiR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma (2013) J. Exp. Med., 210, pp. 789-803Laplante, M., Sabatini, D.M., MTOR signaling in growth control and disease (2012) Cell, 149, pp. 274-293Brennecke, J., Stark, A., Russell, R.B., Cohen, S.M., Principles of microRNA-target recognition (2005) PLoS Biol., 3, p. 85Sun, J., Chen, Z., Tan, X., Zhou, F., Tan, F., Gao, Y., MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma (2013) Med. Oncol. Northwood Lond. Engl., 30, p. 411Guertin, D.A., Sabatini, D.M., An expanding role for mTOR in cancer (2005) Trends Mol. Med., 11, pp. 353-361Cui, L., Zhou, H., Zhao, H., Zhou, Y., Xu, R., Xu, X., MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma (2012) BMC Cancer, 12, p. 546Iwaya, T., Yokobori, T., Nishida, N., Kogo, R., Sudo, T., Tanaka, F., Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway (2012) Carcinogenesis, 33, pp. 2391-2397Saito, Y.D., Jensen, A.R., Salgia, R., Posadas, E.M., Fyn: A novel molecular target in cancer (2010) Cancer, 116, pp. 1629-1637Ninio-Many, L., Grossman, H., Shomron, N., Chuderland, D., Shalgi, R., MicroRNA-125a-3p reduces cell proliferation and migration by targeting Fyn (2013) J. Cell Sci., 126, pp. 2867-2876Parsons, J.T., Martin, K.H., Slack, J.K., Taylor, J.M., Weed, S.A., Focal adhesion kinase: A regulator of focal adhesion dynamics and cell movement (2000) Oncogene, 19, pp. 5606-5613Ma, W.W., Development of focal adhesion kinase inhibitors in cancer therapy (2011) Anticancer Agents Med. Chem., 11, pp. 638-642Kong, X., Li, G., Yuan, Y., He, Y., Wu, X., Zhang, W., MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression (2012) PloS One, 7, p. 41523Wu, D., Wang, Y., Fan, L., Luo, H., Han, B., Sun, L., MicroRNA-7 regulates glioblastoma cell invasion via targeting focal adhesion kinase expression (2011) Chin. Med. J. (Engl.), 124, pp. 2616-2621Ebert, M.S., Sharp, P.A., Roles for microRNAs in conferring robustness to biological processes (2012) Cell, 149, pp. 515-524Loftus, J.C., Ross, J.T.D., Paquette, K.M., Paulino, V.M., Nasser, S., Yang, Z., MiRNA expression profiling in migrating glioblastoma cells: Regulation of cell migration and invasion by miR-23b via targeting of Pyk2 (2012) PloS One, 7, p. 39818Liu, R.-F., Xu, X., Huang, J., Fei, Q.-L., Chen, F., Li, Y.-D., Down-regulation of miR-517a and miR-517c promotes proliferation of hepatocellular carcinoma cells via targeting Pyk2 (2013) Cancer Lett., 329, pp. 164-173Bokoch, G.M., Biology of the p21-activated kinases (2003) Annu. Rev. Biochem., 72, pp. 743-781Kumar, R., Gururaj, A.E., Barnes, C.J., P21-activated kinases in cancer (2006) Nat. Rev. Cancer, 6, pp. 459-471Balasenthil, S., Sahin, A.A., Barnes, C.J., Wang, R.-A., Pestell, R.G., Vadlamudi, R.K., P21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells (2004) J. Biol. Chem., 279, pp. 1422-1428Callow, M.G., Clairvoyant, F., Zhu, S., Schryver, B., Whyte, D.B., Bischoff, J.R., Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines (2002) J. Biol. Chem., 277, pp. 550-558Reddy, S.D.N., Ohshiro, K., Rayala, S.K., Kumar, R., MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions (2008) Cancer Res., 68, pp. 8195-8200Pellegrino, L., Stebbing, J., Braga, V.M., Frampton, A.E., Jacob, J., Buluwela, L., MiR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts (2013) Nucleic Acids Res., 41, pp. 5400-5412Wang, Z., Zhang, X., Yang, Z., Du, H., Wu, Z., Gong, J., MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells (2012) Biochem. Biophys. Res. Commun., 427, pp. 444-449Rath, N., Olson, M.F., Rho-associated kinases in tumorigenesis: Re-considering ROCK inhibition for cancer therapy (2012) EMBO Rep., 13, pp. 900-908Mendell, J.T., Olson, E.N., MicroRNAs in stress signaling and human disease (2012) Cell, 148, pp. 1172-1187Lin, S.-L., Chiang, A., Chang, D., Ying, S.-Y., Loss of mir-146a function in hormone-refractory prostate cancer (2008) RNA N. Y., 14, pp. 417-424Cimino, D., De Pittà, C., Orso, F., Zampini, M., Casara, S., Penna, E., MiR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1 (2013) FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 27, pp. 1223-1235Lynch, J., Fay, J., Meehan, M., Bryan, K., Watters, K.M., Murphy, D.M., MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway (2012) Carcinogenesis, 33, pp. 976-985Ueno, K., Hirata, H., Shahryari, V., Chen, Y., Zaman, M.S., Singh, K., Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma (2011) Br. J. Cancer, 104, pp. 308-315Majid, S., Dar, A.A., Saini, S., Shahryari, V., Arora, S., Zaman, M.S., MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer (2012) PloS One, 7, p. 46743Zheng, F., Liao, Y.-J., Cai, M.-Y., Liu, Y.-H., Liu, T.-H., Chen, S.-P., The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2 (2012) Gut, 61, pp. 278-289Jiang, L., Liu, X., Kolokythas, A., Yu, J., Wang, A., Heidbreder, C.E., Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma (2010) Int. J. Cancer, 127, pp. 505-512Wong, C.C.-L., Wong, C.-M., Tung, E.K.-K., Au, S.L.-K., Lee, J.M.-F., Poon, R.T.-P., The microRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating Rho-kinase 2 (2011) Gastroenterology, 140, pp. 322-331Baserga, R., Peruzzi, F., Reiss, K., The IGF-1 receptor in cancer biology (2003) Int. J. Cancer, 107, pp. 873-877Cao, Z., Liu, L.-Z., Dixon, D.A., Zheng, J.Z., Chandran, B., Jiang, B.-H., Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells (2007) Cell Signal., 19, pp. 1542-1553Bartel, D.P., MicroRNAs: Target recognition and regulatory functions (2009) Cell, 136, pp. 215-233Jiang, L., Liu, X., Chen, Z., Jin, Y., Heidbreder, C.E., Kolokythas, A., MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells (2010) Biochem. J., 432, pp. 199-205Chen, L., Wang, Q., Wang, G., Wang, H., Huang, Y., Liu, X., MiR-16 inhibits cell proliferation by targeting IGF1R andYamamoto, H., Adachi, Y., Taniguchi, H., Kunimoto, H., Nosho, K., Suzuki, H., Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer (2012) World J. Gastroenterol. WJG, 18, pp. 2745-2755Ali, A.S., Ahmad, A., Ali, S., Bao, B., Philip, P.A., Sarkar, F.H., The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis (2013) J. Cell. Physiol., 228, pp. 36-42Vickers, K.C., Remaley, A.T., Lipid-based carriers of microRNAs and intercellular communication (2012) Curr. Opin. Lipidol., 23, pp. 91-97Berger, F., Reiser, M.F., Micro-RNAs as potential new molecular biomarkers in oncology: Have they reached relevance for the clinical imaging sciences? (2013) Theranostics, 3, pp. 943-952Jarry, J., Schadendorf, D., Greenwood, C., Spatz, A., Van Kempen, L.C., The validity of circulating microRNAs in oncology: Five years of challenges and contradictions (2014) Mol. Oncol., 8, pp. 819-829Tang, X., Li, M., Tucker, L., Ramratnam, B., Glycogen synthase kinase 3 beta (GSK3β) phosphorylates the RNAase III enzyme Drosha at S300 and S302 (2011) PloS One, 6, p. 20391Feng, Y., Zhang, X., Song, Q., Li, T., Zeng, Y., Drosha processing controls the specificity and efficiency of global microRNA expression (2011) Biochim. Biophys. Acta, 1809, pp. 700-707Haase, A.D., Jaskiewicz, L., Zhang, H., Lainé, S., Sack, R., Gatignol, A., TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing (2005) EMBO Rep., 6, pp. 961-967Lee, Y., Hur, I., Park, S.-Y., Kim, Y.-K., Suh, M.R., Kim, V.N., The role of PACT in the RNA silencing pathway (2006) EMBO J., 25, pp. 522-532Chendrimada, T.P., Gregory, R.I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing (2005) Nature, 436, pp. 740-744Paroo, Z., Ye, X., Chen, S., Liu, Q., Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling (2009) Cell, 139, pp. 112-122Mito, J.K., Min, H.D., Ma, Y., Carter, J.E., Brigman, B.E., Dodd, L., Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma (2013) J. Pathol., 229, pp. 132-140Ferreira, P.A., Ruela-De-Sousa, R.R., Queiroz, K.C.S., Souza, A.C.S., Milani, R., Pilli, R.A., Knocking down low molecular weight protein tyrosine phosphatase (LMW-PTP) reverts chemoresistance through inactivation of Src and Bcr-Abl proteins (2012) PLoS ONE, 7, p. 44312Van Rooij, E., Sutherland, L.B., Qi, X., Richardson, J.A., Hill, J., Olson, E.N., Control of stress-dependent cardiac growth and gene expression by a microRNA (2007) Science, 316, pp. 575-579Baccarini, A., Chauhan, H., Gardner, T.J., Jayaprakash, A.D., Sachidanandam, R., Brown, B.D., Kinetic analysis reveals the fate of a microRNA following target regulation in mammalian cells (2011) Curr. Biol. CB, 21, pp. 369-376Gantier, M.P., McCoy, C.E., Rusinova, I., Saulep, D., Wang, D., Xu, D., Analysis of microRNA turnover in mammalian cells following Dicer1 ablation (2011) Nucleic Acids Res., 39, pp. 5692-5703Lee, E.J., Baek, M., Gusev, Y., Brackett, D.J., Nuovo, G.J., Schmittgen, T.D., Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors (2008) RNA N.Y., 14, pp. 35-42Hwang, H.-W., Wentzel, E.A., Mendell, J.T., A hexanucleotide element directs microRNA nuclear import (2007) Science, 315, pp. 97-100Marcinowski, L., Tanguy, M., Krmpotic, A., Rädle, B., Lisnić, V.J., Tuddenham, L., Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo (2012) PLoS Pathog., 8, p. 1002510Avraham, R., Sas-Chen, A., Manor, O., Steinfeld, I., Shalgi, R., Tarcic, G., EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors (2010) Sci. Signal., 3, p. 43Tirasophon, W., Welihinda, A.A., Kaufman, R.J., A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in