Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers

Ammad Ahmad Farooqi; Rukset Attar; Muhammad Zahid Qureshi; Sundas Fayyaz; Muhammad Imran Sohail; Uteuliyev Yerzhan Sabitaliyevich; Sadykov Bolat Nurmurzayevich; Armida Yelekenova; Ilhan Yaylim; Nada Alaaeddine

doi:10.14715/cmb/2017.64.15.1

Issue

Vol. 64 No. 15: Issue 15

Issue Published : January 1, 2019

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Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers

https://doi.org/10.14715/cmb/2017.64.15.1

Ammad Ahmad Farooqi

Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore

Rukset Attar

Department of Obstetrics and Gynecology, Yeditepe University, Turkey

Muhammad Zahid Qureshi

Department of Chemistry, GCU Lahore, Pakistan

Sundas Fayyaz

Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan

Muhammad Imran Sohail

Department of Zoology, GCU Lahore, Pakistan

Uteuliyev Yerzhan Sabitaliyevich

Kazakhstan Medical University "KSPH", Kazakhstan

Sadykov Bolat Nurmurzayevich

City Clinical Hospital No.5 in Almaty, Kazakhstan

Armida Yelekenova

Department of Obstetrics and Gynecology, Astana Medical University, Kazakhstan

Ilhan Yaylim

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

Nada Alaaeddine

Laboratoire d'immunologie cellulaire et moleculaire, Centre hospitalier de l'universite de Montreal, Tour Viger, 900 rue Saint-Denis, Montreal, Montreal H2X0A9, Quebec, Canada

Corresponding Author(s) : Ammad Ahmad Farooqi

ammadfarooqi@rlmclahore.com

Cellular and Molecular Biology, Vol. 64 No. 15: Issue 15
Article Published : December 31, 2018

Abstract

Based on the exciting insights gleaned from decades of ground-breaking research, it has become evident that deregulated signaling pathways play instrumental role in cancer development and progression. Interestingly discovery of non-coding RNAs has revolutionized our understanding related to transcription, post-transcription and translation. Modern era has witnessed landmark discoveries in the field of molecular cancer and non-coding RNA biology has undergone tremendous broadening. There has been an exponential growth in the list of publications related to non-coding RNAs and overwhelmingly increasing classes of non-coding RNAs are adding new layers of complexity to already complicated nature of cancer. Regulation of TGF/SMAD signaling by miRNAs and LncRNAs has opened new horizons for therapeutic targeting of TGF/SMAD pathway. In this review we have set spotlight on central role of LncRNAs in modulation of TGF/SMAD pathway. Major proportion of the available evidence is underlining positive role of LncRNAs in contextual regulation of TGF/SMAD pathway. LncRNAs are vital to these regulatory networks because they provide a background support to make the TGF/SMAD mediated intracellular signaling more smooth or make transduction cascade more flexible in response to cues from extracellular environment. Therefore, in accordance with this notion, MALAT1, OIP5-AS1, MIR100HG, HOTAIR, ANRIL, PVT1, AFAP1-AS1, SPRY4-IT, ZEB2NAT, TUG1 and Lnc-SNHG1 have been reported to positively regulate TGF/SMAD signaling. In this review, we have focused on the regulation of TGF/SMAD signaling by LncRNAs and how these non-coding RNAs can be therapeutically exploited. Short-interfering RNA (siRNA) and natural products are currently being tested for efficacy against different LncRNAs. Nanotechnological strategies to efficiently deliver LncRNA-targeting siRNAs are also currently being investigated in different cancers.

Keywords

Cancer TGF SMAD Signaling LncRNA MALAT1 HOTAIR ANRIL.

Farooqi, A. A., Attar, R., Qureshi, M. Z., Fayyaz, S., Sohail, M. I., Sabitaliyevich, U. Y., Nurmurzayevich, S. B., Yelekenova, A., Yaylim, I., & Alaaeddine, N. (2018). Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers. Cellular and Molecular Biology, 64(15), 1–6. https://doi.org/10.14715/cmb/2017.64.15.1

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References

References:
Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007 Dec;8(12):970-82.
Lönn P, Morén A, Raja E, Dahl M, Moustakas A. Regulating the stability of TGFbeta receptors and Smads. Cell Res. 2009 Jan;19(1):21-35. doi: 10.1038/cr.2008.308.
Ikushima H, Miyazono K. TGFbeta signalling: a complex web in cancer progression. Nat Rev Cancer. 2010 Jun;10(6):415-24. doi: 10.1038/nrc2853.
Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018 Jan;18(1):5-18. doi: 10.1038/nrc.2017.99.
Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012 Feb 15;482(7385):339-46. doi: 10.1038/nature10887.
Matsui M, Corey DR. Non-coding RNAs as drug targets. Nat Rev Drug Discov. 2017 Mar;16(3):167-179. doi: 10.1038/nrd.2016.117.
Tang Y, He Y, Zhang P, Wang J, Fan C, Yang L, Xiong F, Zhang S, Gong Z, Nie S, Liao Q, Li X, Li X, Li Y, Li G, Zeng Z, Xiong W, Guo C. LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis. Mol Cancer. 2018 Apr 4;17(1):77. doi: 10.1186/s12943-018-0825-x.
Janakiraman H, House RP, Gangaraju VK, Diehl JA, Howe PH, Palanisamy V.The Long (lncRNA) and Short (miRNA) of It: TGFÎ²-Mediated Control of RNA-Binding Proteins and Noncoding RNAs. Mol Cancer Res. 2018 Apr;16(4):567-579. doi: 10.1158/1541-7786.MCR-17-0547.
Lin C, Yang L. Long Noncoding RNA in Cancer: Wiring Signaling Circuitry. Trends Cell Biol. 2018 Apr;28(4):287-301. doi: 10.1016/j.tcb.2017.11.008.
Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017 Oct 12;36(41):5661-5667. doi: 10.1038/onc.2017.184.
Hu J, Zhang L, Mei Z, Jiang Y, Yi Y, Liu L, Meng Y, Zhou L, Zeng J, Wu H, Jiang X. Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer. Cell Physiol Biochem. 2018;47(2):654-666. doi: 10.1159/000490020.
Hu J, Meng Y, Yu T, Hu L, Mao M. Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth. Oncotarget. 2015 May 20;6(14):12174-87.
Du M, Chen W, Zhang W, Tian XK, Wang T, Wu J, Gu J, Zhang N, Lu ZW, Qian LX, Fei Q, Wang Y, Peng F, He X, Yin L. TGF-? regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma. Biomed Pharmacother. 2018 Mar;99:688-696. doi: 10.1016/j.biopha.2018.01.120.
Xiang Y, Zhang Y, Tang Y, Li Q. MALAT1 Modulates TGF-Î²1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145. Cell Physiol Biochem. 2017;42(1):357-372. doi: 10.1159/000477479.
Li Q, Pan X, Wang X, Jiao X, Zheng J, Li Z, Huo Y. Long noncoding RNA MALAT1 promotes cell proliferation through suppressing miR-205 and promoting SMAD4 expression in osteosarcoma. Oncotarget. 2017 Sep 6;8(63):106648-106660. doi: 10.18632/oncotarget.20678.
Chen X, Xiong D, Yang H, Ye L, Mei S, Wu J, Chen S, Shang X, Wang K, Huang L. Long noncoding RNA OPA-interacting protein 5 antisense transcript 1 upregulated SMAD3 expression to contribute to metastasis of cervical cancer by sponging miR-143-3p. J Cell Physiol. 2018 Oct 20. doi: 10.1002/jcp.27336.
Zhang C, Hao Y, Wang Y, Xu J, Teng Y, Yang X. TGF-Î²/SMAD4-Regulated LncRNA-LINP1 Inhibits Epithelial-Mesenchymal Transition in Lung Cancer. Int J Biol Sci. 2018 Sep 7;14(12):1715-1723. doi: 10.7150/ijbs.27197.
Ottaviani S, Stebbing J, Frampton AE, Zagorac S, Krell J, de Giorgio A, Trabulo SM, Nguyen VTM, Magnani L, Feng H, Giovannetti E, Funel N, Gress TM, Jiao LR, Lombardo Y, Lemoine NR, Heeschen C, Castellano L. TGF-Î² induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression. Nat Commun. 2018 May 10;9(1):1845. doi: 10.1038/s41467-018-03962-x.
Ren Y, Jia HH, Xu YQ, Zhou X, Zhao XH, Wang YF, Song X, Zhu ZY, Sun T, Dou Y, Tian WP, Zhao XL, Kang CS, Mei M. Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR stimulated by TGF-íŸ1 secretion. Mol Cancer. 2018;17(1):5. doi: 10.1186/s12943-018-0758-4.
Zhao B, Lu YL, Yang Y, Hu LB, Bai Y, Li RQ, Zhang GY, Li J, Bi CW, Yang LB, Hu C, Lei YH, Wang QL, Liu ZM. Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-Î²1/ Smad signaling pathway. Cancer Biomark. 2018 Feb 14;21(3):613-620. doi: 10.3233/CBM-170683.
Zhao JJ, Hao S, Wang LL, Hu CY, Zhang S, Guo LJ, Zhang G, Gao B, Jiang Y, Tian WG, Luo DL. Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-Î²/Smad signaling pathway. Oncotarget. 2016 Sep 6;7(36):57903-57918. doi: 10.18632/oncotarget.11087.
Zhang X, Feng W, Zhang J, Ge L, Zhang Y, Jiang X, Peng W, Wang D, Gong A, Xu M. Long non"‘coding RNA PVT1 promotes epithelial"‘mesenchymal transition via the TGF"‘Î²/Smad pathway in pancreatic cancer cells. Oncol Rep. 2018 Aug;40(2):1093-1102. doi: 10.3892/or.2018.6462.
Liu E, Liu Z, Zhou Y, Mi R, Wang D. Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways. Int J Clin Exp Med. 2015 Nov 15;8(11):20565-72. eCollection 2015.
Wang ZY, Hu M, Dai MH, Xiong J, Zhang S, Wu HJ, Zhang SS, Gong ZJ. Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/Î²-catenin signaling pathway. Mol Cancer. 2018 Jan 8;17(1):3. doi: 10.1186/s12943-017-0752-2.
Zhou H, Sun Z, Li S, Wang X, Zhou X. LncRNA SPRY4-IT was concerned with the poor prognosis and contributed to the progression of thyroid cancer. Cancer Gene Ther. 2018 Feb;25(1-2):39-46. doi: 10.1038/s41417-017-0003-0.
Zhuang J, Lu Q, Shen B, Huang X, Shen L, Zheng X, Huang R, Yan J, Guo H. TGFÎ²1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci Rep. 2015 Jul 8;5:11924. doi: 10.1038/srep11924.
Qin CF, Zhao FL. Long non-coding RNA TUG1 can promote proliferation and migration of pancreatic cancer via EMT pathway. Eur Rev Med Pharmacol Sci. 2017 May;21(10):2377-2384.
Wang H, Wang G, Gao Y, Zhao C, Li X, Zhang F, Jiang C, Wu B. Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/Î²-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive Pituitary Tumors. Cell Physiol Biochem. 2018;48(3):1291-1303. doi: 10.1159/000492089.
Deng Y, Zhao F, Zhang Z, Sun F, Wang M. Long Noncoding RNA SNHG7 Promotes the Tumor Growth and Epithelial-to-Mesenchymal Transition via Regulation of miR-34a Signals in Osteosarcoma. Cancer Biother Radiopharm. 2018 Jul 10. doi: 10.1089/cbr.2018.2503.
Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K, Miyazono K, Koinuma D. Long noncoding RNA NORAD regulates transforming growth factor-Î² signaling and epithelial-to-mesenchymal transition-like phenotype. Cancer Sci. 2018 Jul;109(7):2211-2220. doi: 10.1111/cas.13626.
Hao Y, Yang X, Zhang D, Luo J, Chen R. Long noncoding RNA LINC01186, regulated by TGF-Î²/SMAD3, inhibits migration and invasion through Epithelial-Mesenchymal-Transition in lung cancer. Gene. 2017 Apr 15;608:1-12. doi: 10.1016/j.gene.2017.01.023.
Zhu F, Zhang X, Yu Q, Han G, Diao F, Wu C, Zhang Y. LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression. J Cell Biochem. 2018 Jun;119(6):4496-4505. doi: 10.1002/jcb.26556.
Li RQ, Wu W, Song HQ, Ren Y, Yang M, Li J, Xu FJ. Well-defined reducible cationic nanogels based on functionalized low-molecular-weight PGMA for effective pDNA and siRNA delivery. Acta Biomater. 2016 Sep 1;41:282-92. doi: 10.1016/j.actbio.2016.06.006.
Kim SS, Harford JB, Moghe M, Rait A, Pirollo KF, Chang EH. Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide. Nucleic Acids Res. 2018 Feb 16;46(3):1424-1440. doi: 10.1093/nar/gkx1221.
Sophia J, Kowshik J, Dwivedi A, Bhutia SK, Manavathi B, Mishra R, Nagini S. Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3Î² signalling pathway in oral cancer. Cell Death Dis. 2018 Oct 23;9(11):1087. doi: 10.1038/s41419-018-1126-4.
Pedram Fatemi R, Salah-Uddin S, Modarresi F, Khoury N, Wahlestedt C, Faghihi MA. Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen. J Biomol Screen. 2015 Oct;20(9):1132-41. doi: 10.1177/1087057115594187.

References

References:

Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 2007 Dec;8(12):970-82.

Lönn P, Morén A, Raja E, Dahl M, Moustakas A. Regulating the stability of TGFbeta receptors and Smads. Cell Res. 2009 Jan;19(1):21-35. doi: 10.1038/cr.2008.308.

Ikushima H, Miyazono K. TGFbeta signalling: a complex web in cancer progression. Nat Rev Cancer. 2010 Jun;10(6):415-24. doi: 10.1038/nrc2853.

Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018 Jan;18(1):5-18. doi: 10.1038/nrc.2017.99.

Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012 Feb 15;482(7385):339-46. doi: 10.1038/nature10887.

Matsui M, Corey DR. Non-coding RNAs as drug targets. Nat Rev Drug Discov. 2017 Mar;16(3):167-179. doi: 10.1038/nrd.2016.117.

Tang Y, He Y, Zhang P, Wang J, Fan C, Yang L, Xiong F, Zhang S, Gong Z, Nie S, Liao Q, Li X, Li X, Li Y, Li G, Zeng Z, Xiong W, Guo C. LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis. Mol Cancer. 2018 Apr 4;17(1):77. doi: 10.1186/s12943-018-0825-x.

Janakiraman H, House RP, Gangaraju VK, Diehl JA, Howe PH, Palanisamy V.The Long (lncRNA) and Short (miRNA) of It: TGFÎ²-Mediated Control of RNA-Binding Proteins and Noncoding RNAs. Mol Cancer Res. 2018 Apr;16(4):567-579. doi: 10.1158/1541-7786.MCR-17-0547.

Lin C, Yang L. Long Noncoding RNA in Cancer: Wiring Signaling Circuitry. Trends Cell Biol. 2018 Apr;28(4):287-301. doi: 10.1016/j.tcb.2017.11.008.

Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017 Oct 12;36(41):5661-5667. doi: 10.1038/onc.2017.184.

Hu J, Zhang L, Mei Z, Jiang Y, Yi Y, Liu L, Meng Y, Zhou L, Zeng J, Wu H, Jiang X. Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer. Cell Physiol Biochem. 2018;47(2):654-666. doi: 10.1159/000490020.

Hu J, Meng Y, Yu T, Hu L, Mao M. Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth. Oncotarget. 2015 May 20;6(14):12174-87.

Du M, Chen W, Zhang W, Tian XK, Wang T, Wu J, Gu J, Zhang N, Lu ZW, Qian LX, Fei Q, Wang Y, Peng F, He X, Yin L. TGF-? regulates the ERK/MAPK pathway independent of the SMAD pathway by repressing miRNA-124 to increase MALAT1 expression in nasopharyngeal carcinoma. Biomed Pharmacother. 2018 Mar;99:688-696. doi: 10.1016/j.biopha.2018.01.120.

Xiang Y, Zhang Y, Tang Y, Li Q. MALAT1 Modulates TGF-Î²1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145. Cell Physiol Biochem. 2017;42(1):357-372. doi: 10.1159/000477479.

Li Q, Pan X, Wang X, Jiao X, Zheng J, Li Z, Huo Y. Long noncoding RNA MALAT1 promotes cell proliferation through suppressing miR-205 and promoting SMAD4 expression in osteosarcoma. Oncotarget. 2017 Sep 6;8(63):106648-106660. doi: 10.18632/oncotarget.20678.

Chen X, Xiong D, Yang H, Ye L, Mei S, Wu J, Chen S, Shang X, Wang K, Huang L. Long noncoding RNA OPA-interacting protein 5 antisense transcript 1 upregulated SMAD3 expression to contribute to metastasis of cervical cancer by sponging miR-143-3p. J Cell Physiol. 2018 Oct 20. doi: 10.1002/jcp.27336.

Zhang C, Hao Y, Wang Y, Xu J, Teng Y, Yang X. TGF-Î²/SMAD4-Regulated LncRNA-LINP1 Inhibits Epithelial-Mesenchymal Transition in Lung Cancer. Int J Biol Sci. 2018 Sep 7;14(12):1715-1723. doi: 10.7150/ijbs.27197.

Ottaviani S, Stebbing J, Frampton AE, Zagorac S, Krell J, de Giorgio A, Trabulo SM, Nguyen VTM, Magnani L, Feng H, Giovannetti E, Funel N, Gress TM, Jiao LR, Lombardo Y, Lemoine NR, Heeschen C, Castellano L. TGF-Î² induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression. Nat Commun. 2018 May 10;9(1):1845. doi: 10.1038/s41467-018-03962-x.

Ren Y, Jia HH, Xu YQ, Zhou X, Zhao XH, Wang YF, Song X, Zhu ZY, Sun T, Dou Y, Tian WP, Zhao XL, Kang CS, Mei M. Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR stimulated by TGF-íŸ1 secretion. Mol Cancer. 2018;17(1):5. doi: 10.1186/s12943-018-0758-4.

Zhao B, Lu YL, Yang Y, Hu LB, Bai Y, Li RQ, Zhang GY, Li J, Bi CW, Yang LB, Hu C, Lei YH, Wang QL, Liu ZM. Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-Î²1/ Smad signaling pathway. Cancer Biomark. 2018 Feb 14;21(3):613-620. doi: 10.3233/CBM-170683.

Zhao JJ, Hao S, Wang LL, Hu CY, Zhang S, Guo LJ, Zhang G, Gao B, Jiang Y, Tian WG, Luo DL. Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-Î²/Smad signaling pathway. Oncotarget. 2016 Sep 6;7(36):57903-57918. doi: 10.18632/oncotarget.11087.

Zhang X, Feng W, Zhang J, Ge L, Zhang Y, Jiang X, Peng W, Wang D, Gong A, Xu M. Long non"‘coding RNA PVT1 promotes epithelial"‘mesenchymal transition via the TGF"‘Î²/Smad pathway in pancreatic cancer cells. Oncol Rep. 2018 Aug;40(2):1093-1102. doi: 10.3892/or.2018.6462.

Liu E, Liu Z, Zhou Y, Mi R, Wang D. Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways. Int J Clin Exp Med. 2015 Nov 15;8(11):20565-72. eCollection 2015.

Wang ZY, Hu M, Dai MH, Xiong J, Zhang S, Wu HJ, Zhang SS, Gong ZJ. Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/Î²-catenin signaling pathway. Mol Cancer. 2018 Jan 8;17(1):3. doi: 10.1186/s12943-017-0752-2.

Zhou H, Sun Z, Li S, Wang X, Zhou X. LncRNA SPRY4-IT was concerned with the poor prognosis and contributed to the progression of thyroid cancer. Cancer Gene Ther. 2018 Feb;25(1-2):39-46. doi: 10.1038/s41417-017-0003-0.

Zhuang J, Lu Q, Shen B, Huang X, Shen L, Zheng X, Huang R, Yan J, Guo H. TGFÎ²1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci Rep. 2015 Jul 8;5:11924. doi: 10.1038/srep11924.

Qin CF, Zhao FL. Long non-coding RNA TUG1 can promote proliferation and migration of pancreatic cancer via EMT pathway. Eur Rev Med Pharmacol Sci. 2017 May;21(10):2377-2384.

Wang H, Wang G, Gao Y, Zhao C, Li X, Zhang F, Jiang C, Wu B. Lnc-SNHG1 Activates the TGFBR2/SMAD3 and RAB11A/Wnt/Î²-Catenin Pathway by Sponging MiR-302/372/373/520 in Invasive Pituitary Tumors. Cell Physiol Biochem. 2018;48(3):1291-1303. doi: 10.1159/000492089.

Deng Y, Zhao F, Zhang Z, Sun F, Wang M. Long Noncoding RNA SNHG7 Promotes the Tumor Growth and Epithelial-to-Mesenchymal Transition via Regulation of miR-34a Signals in Osteosarcoma. Cancer Biother Radiopharm. 2018 Jul 10. doi: 10.1089/cbr.2018.2503.

Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K, Miyazono K, Koinuma D. Long noncoding RNA NORAD regulates transforming growth factor-Î² signaling and epithelial-to-mesenchymal transition-like phenotype. Cancer Sci. 2018 Jul;109(7):2211-2220. doi: 10.1111/cas.13626.

Hao Y, Yang X, Zhang D, Luo J, Chen R. Long noncoding RNA LINC01186, regulated by TGF-Î²/SMAD3, inhibits migration and invasion through Epithelial-Mesenchymal-Transition in lung cancer. Gene. 2017 Apr 15;608:1-12. doi: 10.1016/j.gene.2017.01.023.

Zhu F, Zhang X, Yu Q, Han G, Diao F, Wu C, Zhang Y. LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression. J Cell Biochem. 2018 Jun;119(6):4496-4505. doi: 10.1002/jcb.26556.

Li RQ, Wu W, Song HQ, Ren Y, Yang M, Li J, Xu FJ. Well-defined reducible cationic nanogels based on functionalized low-molecular-weight PGMA for effective pDNA and siRNA delivery. Acta Biomater. 2016 Sep 1;41:282-92. doi: 10.1016/j.actbio.2016.06.006.

Kim SS, Harford JB, Moghe M, Rait A, Pirollo KF, Chang EH. Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide. Nucleic Acids Res. 2018 Feb 16;46(3):1424-1440. doi: 10.1093/nar/gkx1221.

Sophia J, Kowshik J, Dwivedi A, Bhutia SK, Manavathi B, Mishra R, Nagini S. Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3Î² signalling pathway in oral cancer. Cell Death Dis. 2018 Oct 23;9(11):1087. doi: 10.1038/s41419-018-1126-4.

Pedram Fatemi R, Salah-Uddin S, Modarresi F, Khoury N, Wahlestedt C, Faghihi MA. Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen. J Biomol Screen. 2015 Oct;20(9):1132-41. doi: 10.1177/1087057115594187.

Author biographies is not available.