Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression
<p>Cell plasticity in EMT. Epithelial-mesenchymal transition is a multistep process allowing epithelial cells to acquire mesenchymal phenotype. Upon TGF-β exposure, epithelial cells lose their apical-basal polarity and cellular junctions leading to a loss of cell-cell cohesion. Through a complex and regimented cellular and molecular program, these cells progressively gain mesenchymal features, including cytoskeleton reorganization and proteolytic capacity favoring efficient cell motility.</p> "> Figure 2
<p>The Role of EMT and MET in carcinomas progression. (<b>1</b>) Following carcinogenesis, epithelial tumor cells proliferate to develop primary tumors called carcinoma in situ. In response to acquired mutations and/or exogenous stimuli, tumor cells gain invasive properties allowing them to break the basement membrane. Tumor cells then (<b>2</b>) invade and spread to surrounding tissues and structures and interact with numerous TME factors including cytokine-secreting CAFs, which reinforce EMT and invasion processes (cytoskeleton reorganization and increased proteolytic activity allow cells to degrade and invade the extracellular matrix (ECM)); (<b>3</b>) penetrate the vascular system (intravasation); (<b>4</b>) circulate throughout the body; (<b>5</b>) leave the vascular system to invade distant tissues (extravasation); (<b>6</b>) colonize distant sites through ECM degradation and invasion; and (<b>7</b>) reacquire epithelial phenotypes through MET and proliferate to ultimately form a metastasis.</p> "> Figure 3
<p>(<b>A</b>) Cell morphology and expression of EMT markers<b>:</b> A549 cells pictured after no-treatment (NT), three days of TGFβ treatment (3d), and 5d of TGFβ treatment. Cells begin with a slightly mesenchymal phenotype in the NT, but display a completely mesenchymal phenotype after prolonged exposure to TGFβ. E-cadherin (white) is the epithelial cell marker and vimentin (yellow) is the mesenchymal cell marker. DAPI (blue) is the counterstain used to stain nuclei. HSP90 was used as a loading control. (<b>B</b>) Overview of the experimental Procedure: <b>1</b>. Radioactive orthophosphate was added to cell cultures at onset of experiment. <b>2</b>. Total RNAs were Trizol extracted and all other labeled molecules were removed from sample. <b>3</b>. Labeling of tRNA molecules was confirmed via gel electrophoresis. <b>4</b>. Samples were hybridized to tRNA microarrays and analyzed. (<b>C</b>) Average tRNA expression: The heat map shows the average number of each tRNA (per thousand) that is present across the three conditions. tRNA abundances range from close to 0 to over 60‰. (<b>D</b>) Statistically significant results: The relative tRNA expression, per thousand, of the four tRNA that displayed significant changes in tRNA expression throughout EMT are shown along with standard error bars. Both 3d and 5d were compared to the NT and the statistical significance of those changes can be seen from the dot on the bars. The overall trend of expression for each tRNA is shown below the graph.</p> ">
Abstract
:1. Introduction
2. Cellular Basis of TGF-β-Induced EMT
3. Molecular Mechanisms of TGF-β-Induced EMT
3.1. Transcriptional Regulation of TGF-β-Induced EMT in Tumor Cells
3.2. Post-Transcriptional Regulation of TGF-β-Induced EMT in Tumor Cells
4. Role of Non-Coding RNAs in TGF-β-Induced EMT
4.1. miRNAs
4.2. Long Non-Coding RNAs
4.2.1. LncRNA-ATB
4.2.2. MALAT1
4.2.3. lncRNA-ZEB2NAT
4.2.4. HOTAIR
4.2.5. lncRNA-HIT
4.2.6. MEG3
4.3. Other Non-Coding RNA Species
4.3.1. Circular RNAs
4.3.2. PIWI-interacting RNAs
4.3.3. Small Nucleolar and Small Nuclear RNAs
4.3.4. Transfer RNAs
5. Evidence of Selective Regulation of tRNA Expression during TGF-β-Induced EMT
Acknowledgments
Conflicts of Interest
References
- Nieto, M.A.; Huang, R.Y.-J.; Jackson, R.A.; Thiery, J.P. EMT: 2016. Cell 2016, 166, 21–45. [Google Scholar] [CrossRef] [PubMed]
- Thiery, J.P.; Acloque, H.; Huang, R.Y.J.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139, 871–890. [Google Scholar] [CrossRef] [PubMed]
- Zheng, X.; Carstens, J.L.; Kim, J.; Scheible, M.; Kaye, J.; Sugimoto, H.; Wu, C.-C.; LeBleu, V.S.; Kalluri, R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015, 527, 525–530. [Google Scholar] [CrossRef] [PubMed]
- Fischer, K.R.; Durrans, A.; Lee, S.; Sheng, J.; Li, F.; Wong, S.T.C.; Choi, H.; El Rayes, T.; Ryu, S.; Troeger, J.; et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 2015, 527, 472–476. [Google Scholar] [CrossRef] [PubMed]
- Krebs, A.M.; Mitschke, J.; Lasierra Losada, M.; Schmalhofer, O.; Boerries, M.; Busch, H.; Boettcher, M.; Mougiakakos, D.; Reichardt, W.; Bronsert, P.; et al. The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat. Cell Biol. 2017, 19, 518–529. [Google Scholar] [CrossRef] [PubMed]
- Francart, M.-E.; Lambert, J.; Vanwynsberghe, A.M.; Thompson, E.W.; Bourcy, M.; Polette, M.; Gilles, C. Epithelial-Mesenchymal Plasticity and Circulating Tumor Cells: Travel Companions to Metastases. Dev. Dyn. Off. Publ. Am. Assoc. Anat. 2017. [Google Scholar] [CrossRef] [PubMed]
- Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Investig. 2009, 119, 1420–1428. [Google Scholar] [CrossRef] [PubMed]
- Smith, B.N.; Bhowmick, N.A. Role of EMT in Metastasis and Therapy Resistance. J. Clin. Med. 2016, 5, 17. [Google Scholar] [CrossRef] [PubMed]
- Schedin, P.; Borges, V. Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women’s breast cancer. Breast Cancer Res. BCR 2009, 11, 102. [Google Scholar] [CrossRef] [PubMed]
- Kalluri, R.; Zeisberg, M. Fibroblasts in cancer. Nat. Rev. Cancer 2006, 6, 392–401. [Google Scholar] [CrossRef] [PubMed]
- Lamouille, S.; Xu, J.; Derynck, R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol. 2014, 15, 178–196. [Google Scholar] [CrossRef] [PubMed]
- Massagué, J. TGFβ in Cancer. Cell 2008, 134, 215–230. [Google Scholar] [CrossRef] [PubMed]
- Bourcy, M.; Suarez-Carmona, M.; Lambert, J.; Francart, M.-E.; Schroeder, H.; Delierneux, C.; Skrypek, N.; Thompson, E.W.; Jérusalem, G.; Berx, G.; et al. Tissue Factor Induced by Epithelial-Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells. Cancer Res. 2016, 76, 4270–4282. [Google Scholar] [CrossRef] [PubMed]
- Derynck, R.; Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 2003, 425, 577–584. [Google Scholar] [CrossRef] [PubMed]
- Valcourt, U.; Kowanetz, M.; Niimi, H.; Heldin, C.-H.; Moustakas, A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol. Biol. Cell 2005, 16, 1987–2002. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Liu, L.; Wang, Y.; Zhao, G.; Xie, R.; Liu, C.; Xiao, X.; Wu, K.; Nie, Y.; Zhang, H.; et al. KLF8 involves in TGF-beta-induced EMT and promotes invasion and migration in gastric cancer cells. J. Cancer Res. Clin. Oncol. 2013, 139, 1033–1042. [Google Scholar] [CrossRef] [PubMed]
- Larocca, C.; Cohen, J.R.; Fernando, R.I.; Huang, B.; Hamilton, D.H.; Palena, C. An autocrine loop between TGF-β1 and the transcription factor Brachyury controls the transition of human carcinoma cells into a mesenchymal phenotype. Mol. Cancer Ther. 2013, 12. [Google Scholar] [CrossRef] [PubMed]
- Hardin, H.; Guo, Z.; Shan, W.; Montemayor-Garcia, C.; Asioli, S.; Yu, X.-M.; Harrison, A.D.; Chen, H.; Lloyd, R.V. The Roles of the Epithelial-Mesenchymal Transition Marker PRRX1 and miR-146b-5p in Papillary Thyroid Carcinoma Progression. Am. J. Pathol. 2014, 184, 2342–2354. [Google Scholar] [CrossRef] [PubMed]
- Batlle, E.; Sancho, E.; Francí, C.; Domínguez, D.; Monfar, M.; Baulida, J.; García De Herreros, A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2000, 2, 84–89. [Google Scholar] [CrossRef] [PubMed]
- Cano, A.; Pérez-Moreno, M.A.; Rodrigo, I.; Locascio, A.; Blanco, M.J.; del Barrio, M.G.; Portillo, F.; Nieto, M.A. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2000, 2, 76–83. [Google Scholar] [CrossRef] [PubMed]
- Xiang, J.; Fu, X.; Ran, W.; Wang, Z. Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer. Oncogenesis 2017, 6, e284. [Google Scholar] [CrossRef] [PubMed]
- Yao, B.; Zhao, J.; Li, Y.; Li, H.; Hu, Z.; Pan, P.; Zhang, Y.; Du, E.; Liu, R.; Xu, Y. Elf5 inhibits TGF-β-driven epithelial-mesenchymal transition in prostate cancer by repressing SMAD3 activation. Prostate 2015, 75, 872–882. [Google Scholar] [CrossRef] [PubMed]
- Cardenas, H.; Vieth, E.; Lee, J.; Segar, M.; Liu, Y.; Nephew, K.P.; Matei, D. TGF-β induces global changes in DNA methylation during the epithelial-to-mesenchymal transition in ovarian cancer cells. Epigenetics 2014, 9, 1461–1472. [Google Scholar] [CrossRef] [PubMed]
- Serrano-Gomez, S.J.; Maziveyi, M.; Alahari, S.K. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications. Mol. Cancer 2016, 15, 18. [Google Scholar] [CrossRef] [PubMed]
- Roche, J.; Nasarre, P.; Gemmill, R.; Baldys, A.; Pontis, J.; Korch, C.; Guilhot, J.; Ait-Si-Ali, S.; Drabkin, H. Global Decrease of Histone H3K27 Acetylation in ZEB1-Induced Epithelial to Mesenchymal Transition in Lung Cancer Cells. Cancers 2013, 5, 334–356. [Google Scholar] [CrossRef] [PubMed]
- Bedi, U.; Mishra, V.K.; Wasilewski, D.; Scheel, C.; Johnsen, S.A. Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer. Oncotarget 2014, 5, 2016–2029. [Google Scholar] [CrossRef] [PubMed]
- De Craene, B.; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 2013, 13, 97–110. [Google Scholar] [CrossRef] [PubMed]
- Evdokimova, V.; Tognon, C.; Ng, T.; Ruzanov, P.; Melnyk, N.; Fink, D.; Sorokin, A.; Ovchinnikov, L.P.; Davicioni, E.; Triche, T.J.; et al. Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell 2009, 15, 402–415. [Google Scholar] [CrossRef] [PubMed]
- Chaudhury, A.; Hussey, G.S.; Ray, P.S.; Jin, G.; Fox, P.L.; Howe, P.H. TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nat. Cell Biol. 2010, 12, 286–293. [Google Scholar] [CrossRef] [PubMed]
- Hussey, G.S.; Chaudhury, A.; Dawson, A.E.; Lindner, D.J.; Knudsen, C.R.; Wilce, M.C.J.; Merrick, W.C.; Howe, P.H. Identification of an mRNP Complex Regulating Tumorigenesis at the Translational Elongation Step. Mol. Cell 2011, 41, 419–431. [Google Scholar] [CrossRef] [PubMed]
- Grelet, S.; Andries, V.; Polette, M.; Gilles, C.; Staes, K.; Martin, A.-P.; Kileztky, C.; Terryn, C.; Dalstein, V.; Cheng, C.-W.; et al. The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition. J. Pathol. 2015, 237, 25–37. [Google Scholar] [CrossRef] [PubMed]
- Hussey, G.S.; Link, L.A.; Brown, A.S.; Howley, B.V.; Chaudhury, A.; Howe, P.H. Establishment of a TGFβ-Induced Post-Transcriptional EMT Gene Signature. PLOS ONE 2012, 7, e52624. [Google Scholar] [CrossRef] [PubMed]
- Bartel, D.P. MicroRNAs: Target recognition and regulatory functions. Cell 2009, 136, 215–233. [Google Scholar] [CrossRef] [PubMed]
- Londin, E.; Loher, P.; Telonis, A.G.; Quann, K.; Clark, P.; Jing, Y.; Hatzimichael, E.; Kirino, Y.; Honda, S.; Lally, M.; et al. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc. Natl. Acad. Sci. USA 2015, 112, E1106–E1115. [Google Scholar] [CrossRef] [PubMed]
- Gregory, P.A.; Bert, A.G.; Paterson, E.L.; Barry, S.C.; Tsykin, A.; Farshid, G.; Vadas, M.A.; Khew-Goodall, Y.; Goodall, G.J. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 2008, 10, 593–601. [Google Scholar] [CrossRef] [PubMed]
- Korpal, M.; Lee, E.S.; Hu, G.; Kang, Y. The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2. J. Biol. Chem. 2008, 283, 14910–14914. [Google Scholar] [CrossRef] [PubMed]
- Brabletz, S.; Brabletz, T. The ZEB/miR-200 feedback loop—A motor of cellular plasticity in development and cancer? EMBO Rep. 2010, 11, 670–677. [Google Scholar] [CrossRef] [PubMed]
- Gregory, P.A.; Bracken, C.P.; Smith, E.; Bert, A.G.; Wright, J.A.; Roslan, S.; Morris, M.; Wyatt, L.; Farshid, G.; Lim, Y.-Y.; et al. An autocrine TGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol. Biol. Cell 2011, 22, 1686–1698. [Google Scholar] [CrossRef] [PubMed]
- Ding, X.; Park, S.I.; McCauley, L.K.; Wang, C.-Y. Signaling between Transforming Growth Factor β (TGF-β) and Transcription Factor SNAI2 Represses Expression of MicroRNA miR-203 to Promote Epithelial-Mesenchymal Transition and Tumor Metastasis. J. Biol. Chem. 2013, 288, 10241–10253. [Google Scholar] [CrossRef] [PubMed]
- Wellner, U.; Schubert, J.; Burk, U.C.; Schmalhofer, O.; Zhu, F.; Sonntag, A.; Waldvogel, B.; Vannier, C.; Darling, D.; zur Hausen, A.; et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat. Cell Biol. 2009, 11, 1487–1495. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.-N.; Yin, J.J.; Abou-Kheir, W.; Hynes, P.G.; Casey, O.M.; Fang, L.; Yi, M.; Stephens, R.M.; Seng, V.; Sheppard-Tillman, H.; et al. MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms. Oncogene 2013, 32, 296–306. [Google Scholar] [CrossRef] [PubMed]
- Meseure, D.; Drak Alsibai, K.; Nicolas, A.; Bieche, I.; Morillon, A. Long Noncoding RNAs as New Architects in Cancer Epigenetics, Prognostic Biomarkers, and Potential Therapeutic Targets. BioMed Res. Int. 2015, 2015, e320214. [Google Scholar] [CrossRef] [PubMed]
- Tay, Y.; Rinn, J.; Pandolfi, P.P. The multilayered complexity of ceRNA crosstalk and competition. Nature 2014, 505, 344–352. [Google Scholar] [CrossRef] [PubMed]
- Yuan, J.; Yang, F.; Wang, F.; Ma, J.; Guo, Y.; Tao, Q.; Liu, F.; Pan, W.; Wang, T.; Zhou, C.; et al. A Long Noncoding RNA Activated by TGF-β Promotes the Invasion-Metastasis Cascade in Hepatocellular Carcinoma. Cancer Cell 2014, 25, 666–681. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Yi, X.-M.; Tang, C.-P.; Ge, J.-P.; Zhang, Z.-Y.; Zhou, W.-Q. Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma. Oncol. Rep. 2016, 36, 10–22. [Google Scholar] [CrossRef] [PubMed]
- Iguchi, T.; Uchi, R.; Nambara, S.; Saito, T.; Komatsu, H.; Hirata, H.; Ueda, M.; Sakimura, S.; Takano, Y.; Kurashige, J.; et al. A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer. Anticancer Res. 2015, 35, 1385–1388. [Google Scholar] [PubMed]
- Ke, L.; Xu, S.-B.; Wang, J.; Jiang, X.-L.; Xu, M.-Q. High expression of long non-coding RNA ATB indicates a poor prognosis and regulates cell proliferation and metastasis in non-small cell lung cancer. Clin. Transl. Oncol. 2017, 19, 599–605. [Google Scholar] [CrossRef] [PubMed]
- Shi, S.-J.; Wang, L.-J.; Yu, B.; Li, Y.-H.; Jin, Y.; Bai, X.-Z. LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget 2015, 6, 11652–11663. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Shen, B.; Tan, M.; Mu, X.; Qin, Y.; Zhang, F.; Liu, Y. TGF-β-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin. Cancer Res. 2014, 20, 1531–1541. [Google Scholar] [CrossRef] [PubMed]
- Shi, X.; Sun, M.; Liu, H.; Yao, Y.; Song, Y. Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 2013, 339, 159–166. [Google Scholar] [CrossRef] [PubMed]
- Ji, P.; Diederichs, S.; Wang, W.; Böing, S.; Metzger, R.; Schneider, P.M.; Tidow, N.; Brandt, B.; Buerger, H.; Bulk, E.; et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 2003, 22, 8031–8041. [Google Scholar] [CrossRef] [PubMed]
- Hirata, H.; Hinoda, Y.; Shahryari, V.; Deng, G.; Nakajima, K.; Tabatabai, Z.L.; Ishii, N.; Dahiya, R. Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. Cancer Res. 2015, 75, 1322–1331. [Google Scholar] [CrossRef] [PubMed]
- Beltran, M.; Puig, I.; Peña, C.; García, J.M.; Álvarez, A.B.; Peña, R.; Bonilla, F.; de Herreros, A.G. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition. Genes Dev. 2008, 22, 756–769. [Google Scholar] [CrossRef] [PubMed]
- Zhuang, J.; Lu, Q.; Shen, B.; Huang, X.; Shen, L.; Zheng, X.; Huang, R.; Yan, J.; Guo, H. TGFβ1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci. Rep. 2015, 5, 11924. [Google Scholar] [CrossRef] [PubMed]
- Gupta, R.A.; Shah, N.; Wang, K.C.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M.-C.; Hung, T.; Argani, P.; Rinn, J.L.; et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464, 1071–1076. [Google Scholar] [CrossRef] [PubMed]
- Davidovich, C.; Zheng, L.; Goodrich, K.J.; Cech, T.R. Promiscuous RNA binding by Polycomb Repressive Complex 2. Nat. Struct. Mol. Biol. 2013, 20, 1250–1257. [Google Scholar] [CrossRef] [PubMed]
- Rinn, J.L.; Kertesz, M.; Wang, J.K.; Squazzo, S.L.; Xu, X.; Brugmann, S.A.; Goodnough, L.H.; Helms, J.A.; Farnham, P.J.; Segal, E.; et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007, 129, 1311–1323. [Google Scholar] [CrossRef] [PubMed]
- Nakagawa, T.; Endo, H.; Yokoyama, M.; Abe, J.; Tamai, K.; Tanaka, N.; Sato, I.; Takahashi, S.; Kondo, T.; Satoh, K. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem. Biophys. Res. Commun. 2013, 436, 319–324. [Google Scholar] [CrossRef] [PubMed]
- Wu, Z.-H.; Wang, X.-L.; Tang, H.-M.; Jiang, T.; Chen, J.; Lu, S.; Qiu, G.-Q.; Peng, Z.-H.; Yan, D.-W. Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer. Oncol. Rep. 2014, 32, 395–402. [Google Scholar] [CrossRef] [PubMed]
- Hajjari, M.; Khoshnevisan, A.; Shin, Y.K. Molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer. Tumour Biol. 2014, 35, 10645–10663. [Google Scholar] [CrossRef] [PubMed]
- Richards, E.J.; Zhang, G.; Li, Z.-P.; Permuth-Wey, J.; Challa, S.; Li, Y.; Kong, W.; Dan, S.; Bui, M.M.; Coppola, D.; Mao, W.-M.; et al. Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia. J. Biol. Chem. 2015, 290, 6857–6867. [Google Scholar] [CrossRef] [PubMed]
- Mondal, T.; Subhash, S.; Vaid, R.; Enroth, S.; Uday, S.; Reinius, B.; Mitra, S.; Mohammed, A.; James, A.R.; Hoberg, E.; et al. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures. Nat. Commun. 2015, 6, 7743. [Google Scholar] [CrossRef] [PubMed]
- Terashima, M.; Tange, S.; Ishimura, A.; Suzuki, T. MEG3 long noncoding RNA contributes to the epigenetic regulation of epithelial-mesenchymal transition in lung cancer cell lines. J. Biol. Chem. 2016, 292, 82–99. [Google Scholar] [CrossRef] [PubMed]
- Dong, Y.; He, D.; Peng, Z.; Peng, W.; Shi, W.; Wang, J.; Li, B.; Zhang, C.; Duan, C. Circular RNAs in cancer: an emerging key player. J. Hematol. Oncol. 2017, 10, 2. [Google Scholar] [CrossRef] [PubMed]
- Bachmayr-Heyda, A.; Reiner, A.T.; Auer, K.; Sukhbaatar, N.; Aust, S.; Bachleitner-Hofmann, T.; Mesteri, I.; Grunt, T.W.; Zeillinger, R.; Pils, D. Correlation of circular RNA abundance with proliferation—Exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci. Rep. 2015, 5, 8057. [Google Scholar] [CrossRef] [PubMed]
- Hansen, T.B.; Kjems, J.; Damgaard, C.K. Circular RNA and miR-7 in cancer. Cancer Res. 2013, 73, 5609–5612. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Yang, J.; Zhou, P.; Le, Y.; Zhou, C.; Wang, S.; Xu, D.; Lin, H.-K.; Gong, Z. Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am. J. Cancer Res. 2015, 5, 472–480. [Google Scholar] [PubMed]
- Hansen, T.B.; Jensen, T.I.; Clausen, B.H.; Bramsen, J.B.; Finsen, B.; Damgaard, C.K.; Kjems, J. Natural RNA circles function as efficient microRNA sponges. Nature 2013, 495, 384–388. [Google Scholar] [CrossRef] [PubMed]
- Weng, W.; Wei, Q.; Toden, S.; Yoshida, K.; Nagasaka, T.; Fujiwara, T.; Cai, S.; Qin, H.; Ma, Y.; Goel, A. Circular RNA ciRS-7—A promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin. Cancer Res. 2017. [Google Scholar] [CrossRef] [PubMed]
- Conn, S.J.; Pillman, K.A.; Toubia, J.; Conn, V.M.; Salmanidis, M.; Phillips, C.A.; Roslan, S.; Schreiber, A.W.; Gregory, P.A.; Goodall, G.J. The RNA Binding Protein Quaking Regulates Formation of circRNAs. Cell 2015, 160, 1125–1134. [Google Scholar] [CrossRef] [PubMed]
- Ng, K.W.; Anderson, C.; Marshall, E.A.; Minatel, B.C.; Enfield, K.S.S.; Saprunoff, H.L.; Lam, W.L.; Martinez, V.D. Piwi-interacting RNAs in cancer: Emerging functions and clinical utility. Mol. Cancer 2016, 15, 5. [Google Scholar] [CrossRef] [PubMed]
- Hashim, A.; Rizzo, F.; Marchese, G.; Ravo, M.; Tarallo, R.; Nassa, G.; Giurato, G.; Santamaria, G.; Cordella, A.; Cantarella, C.; et al. RNA sequencing identifies specific PIWI-interacting small non-coding RNA expression patterns in breast cancer. Oncotarget 2014, 5, 9901–9910. [Google Scholar] [CrossRef] [PubMed]
- Huang, G.; Hu, H.; Xue, X.; Shen, S.; Gao, E.; Guo, G.; Shen, X.; Zhang, X. Altered expression of piRNAs and their relation with clinicopathologic features of breast cancer. Clin. Transl. Oncol. 2013, 15, 563–568. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Ren, Y.; Xu, H.; Pang, D.; Duan, C.; Liu, C. The expression of stem cell protein Piwil2 and piR-932 in breast cancer. Surg. Oncol. 2013, 22, 217–223. [Google Scholar] [CrossRef] [PubMed]
- Rapisuwon, S.; Vietsch, E.E.; Wellstein, A. Circulating biomarkers to monitor cancer progression and treatment. Comput. Struct. Biotechnol. J. 2016, 14, 211–222. [Google Scholar] [CrossRef] [PubMed]
- Su, H.; Xu, T.; Ganapathy, S.; Shadfan, M.; Long, M.; Huang, T.H.-M.; Thompson, I.; Yuan, Z.-M. Elevated snoRNA biogenesis is essential in breast cancer. Oncogene 2014, 33, 1348–1358. [Google Scholar] [CrossRef] [PubMed]
- Ji, X.; Lu, H.; Zhou, Q.; Luo, K. LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis. Elife 2014, 3, e02907. [Google Scholar] [CrossRef] [PubMed]
- Waldron, C.; Lacroute, F. Effect of growth rate on the amounts of ribosomal and transfer ribonucleic acids in yeast. J. Bacteriol. 1975, 122, 855–865. [Google Scholar] [PubMed]
- Goodenbour, J.M.; Pan, T. Diversity of tRNA genes in eukaryotes. Nucleic Acids Res. 2006, 34, 6137–6146. [Google Scholar] [CrossRef] [PubMed]
- Goodarzi, H.; Nguyen, H.C.B.; Zhang, S.; Dill, B.D.; Molina, H.; Tavazoie, S.F. Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression. Cell 2016, 165, 1416–1427. [Google Scholar] [CrossRef] [PubMed]
- Pavon-Eternod, M.; Gomes, S.; Geslain, R.; Dai, Q.; Rosner, M.R.; Pan, T. tRNA over-expression in breast cancer and functional consequences. Nucleic Acids Res. 2009, 37, 7268–7280. [Google Scholar] [CrossRef] [PubMed]
- Rudolph, K.L.M.; Schmitt, B.M.; Villar, D.; White, R.J.; Marioni, J.C.; Kutter, C.; Odom, D.T. Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States. PLOS Genet. 2016, 12, e1006024. [Google Scholar] [CrossRef] [PubMed]
- Geslain, R.; Eriani, G. Regulation of translation dynamic and neoplastic conversion by tRNA and their pieces. Transl. Austin. 2014, 2, e28586. [Google Scholar] [CrossRef] [PubMed]
- Gingold, H.; Pilpel, Y. Determinants of translation efficiency and accuracy. Mol. Syst. Biol. 2011, 7, 481. [Google Scholar] [CrossRef] [PubMed]
- Gingold, H.; Tehler, D.; Christoffersen, N.R.; Nielsen, M.M.; Asmar, F.; Kooistra, S.M.; Christophersen, N.S.; Christensen, L.L.; Borre, M.; Sørensen, K.D.; et al. A dual program for translation regulation in cellular proliferation and differentiation. Cell 2014, 158, 1281–1292. [Google Scholar] [CrossRef] [PubMed]
- Ruijtenberg, S.; van den Heuvel, S. Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. Cell Cycle 2016, 15, 196–212. [Google Scholar] [CrossRef] [PubMed]
- Kumar, S.M.; Liu, S.; Lu, H.; Zhang, H.; Zhang, P.J.; Gimotty, P.A.; Guerra, M.; Guo, W.; Xu, X. Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. Oncogene 2012, 31, 4898–4911. [Google Scholar] [CrossRef] [PubMed]
- Klochendler, A.; Weinberg-Corem, N.; Moran, M.; Swisa, A.; Pochet, N.; Savova, V.; Vikeså, J.; Van de Peer, Y.; Brandeis, M.; Regev, A.; et al. A Transgenic Mouse Marking Live Replicating Cells Reveals In Vivo Transcriptional Program of Proliferation. Dev. Cell 2012, 23, 681–690. [Google Scholar] [CrossRef] [PubMed]
- Cole, C.; Sobala, A.; Lu, C.; Thatcher, S.R.; Bowman, A.; Brown, J.W.S.; Green, P.J.; Barton, G.J.; Hutvagner, G. Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA NY 2009, 15, 2147–2160. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.S.; Shibata, Y.; Malhotra, A.; Dutta, A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009, 23, 2639–2649. [Google Scholar] [CrossRef] [PubMed]
- Saikia, M.; Jobava, R.; Parisien, M.; Putnam, A.; Krokowski, D.; Gao, X.-H.; Guan, B.-J.; Yuan, Y.; Jankowsky, E.; Feng, Z.; et al. Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol. Cell. Biol. 2014, 34, 2450–2463. [Google Scholar] [CrossRef] [PubMed]
- Fu, H.; Feng, J.; Liu, Q.; Sun, F.; Tie, Y.; Zhu, J.; Xing, R.; Sun, Z.; Zheng, X. Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett. 2009, 583, 437–442. [Google Scholar] [CrossRef] [PubMed]
- Kumar, P.; Kuscu, C.; Dutta, A. Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends Biochem. Sci. 2016, 41, 679–689. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.; Lin, Y.; Li, C.; Hu, X.; Liu, Y.; He, M.; Luo, J.; Sun, G.; Wang, T.; Li, W.; et al. MicroRNA-720 promotes in vitro cell migration by targeting Rab35 expression in cervical cancer cells. Cell Biosci. 2015, 5, 56. [Google Scholar] [CrossRef] [PubMed]
- Hua, Y.; Choi, P.-W.; Trachtenberg, A.J.; Ng, A.C.; Kuo, W.P.; Ng, S.-K.; Dinulescu, D.M.; Matzuk, M.M.; Berkowitz, R.S.; Ng, S.-W. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma. Oncotarget 2016, 7, 66077–66086. [Google Scholar] [CrossRef] [PubMed]
- Grelet, S.; McShane, A.; Hok, E.; Tomberlin, J.; Howe, P.H.; Geslain, R. SPOt: A novel and streamlined microarray platform for observing cellular tRNA levels. PLOS ONE 2017, 12, e0177939. [Google Scholar] [CrossRef] [PubMed]
Non-Coding RNA | Relevant Examples | Specific Function | Most Described Targets | Related Cancers | References |
---|---|---|---|---|---|
miRNAs | miR-1 * miR-200 family * miR-205 * miR-203 * | Epithelial maintenance | ZEB1/2↓ Slug↓ Bmi1↓ | Breast Lung Prostate | [5,35,37,39,40] |
LncRNAs | LncRNA-ATB † MALAT1 † lncRNA-ZEB2NAT † HOTAIR † lncRNA-HIT | Tumor cell invasion; Organ colonization; Proliferation; Cancer Stem Cells | ZEB1/2↑ IL-11↑ miR-200↓ miR-205↓ E-cadherin↓ | Prostate Lung Breast Kidney Pancreas Liver Colon Uterus | [44,45,46,47,49,51,52,53,54,55,57,58,59,61] |
MEG3 * | TGF-β pathway regulation | TGFBR1↑ TGFB2↑ SMAD2↑ | Breast | [62,63] | |
circRNAs | CDR1as/ciRS-7 * | miRNA sponge | miRNA-7↓ | Colon | [66,67,69] |
piRNAs | Pir-932 † | Stemness properties | Latexin↓ | Breast | [74] |
snoRNAs snRNAs | 7SK snRNA * | Tumor cell invasion | Slug↓ FOXC2↓ ZEB2↓ Twist1↓ | Breast | [77] |
tRNAs | tRNAGluUUC † | Tumor progression | EXOSC2↓ GRIPAP1↓ | Breast | [80] |
MicroRNA-720 † | Tumor cell motility | Rab35↓ | Uterus | [94] |
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Grelet, S.; McShane, A.; Geslain, R.; Howe, P.H. Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression. Cancers 2017, 9, 75. https://doi.org/10.3390/cancers9070075
Grelet S, McShane A, Geslain R, Howe PH. Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression. Cancers. 2017; 9(7):75. https://doi.org/10.3390/cancers9070075
Chicago/Turabian StyleGrelet, Simon, Ariel McShane, Renaud Geslain, and Philip H. Howe. 2017. "Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression" Cancers 9, no. 7: 75. https://doi.org/10.3390/cancers9070075