LncRNAs as Regulators of the STAT3 Signaling Pathway in Cancer

Journal of Cell and Molecular Research

دوره 13، شماره 2 - شماره پیاپی 26، تیر 2022، صفحه 137-150   

نوع مقاله: Review / Mini-Review

شناسه دیجیتال (DOI): 10.22067/jcmr.2022.75905.1032

نویسندگان

Narges ZadehRashki¹؛ Zahra Shahmohammadi¹؛ ZahraSadat Damrodi¹؛ Sohrab Boozarpour^{* 1}؛ Arezou Negahdari²؛ Nazanin Mansour Moshtaghi³؛ Mehdi Vakilinejad⁴؛ Shaaban Ghalandarayeshi⁵

¹Department of Biology, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Iran

²Radiologist, Dr. Arezou Negahdari Ultrasound-Radiology Clinic, Gonbad Kavous, Iran

³Surgical Oncologists, Dr. Beski Hospital, Gonbad Kavous, Iran

⁴Pathologist, Sina Laboratory, Gonbad Kavous, Iran

⁵Department of Statistics and Mathematics, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Iran

چکیده

Cancer is a disorder of growth control and cell differentiation caused by the abnormal expression of multiple genes. Long non-coding RNAs (lncRNAs) are critical regulators of numerous biological processes, especially in the development of diseases. Abnormal expression of some lncRNAs causes disease, especially cancer, and disease resistance. lncRNAs may act as oncogenes or tumor suppressors and can be used as diagnostic or prognostic markers, and may also have therapeutic potential in cancer treatment. Studies show that many lncRNAs have different effects on cell activity by regulating multiple downstream targets, such as signaling pathways that are signal transducers and activators of transcription 3 (STAT3). The STAT3 signaling pathway is one of the most critical pathways in developing various diseases, including cancer, which plays a vital role in cellular processes, disease onset and progression, and stem cell regeneration by regulating its target genes. STAT3 has been proven to be an anticancer target in various contexts. Types of genes can activate the STAT3 pathway in cancer. Many lncRNAs have been identified associated with the STAT3 pathway that is upstream or downstream. Oncogenic lncRNAs, including PVT1, HOTAIRM1, and MCM3AP-AS1, increase STAT3 expression, while tumor suppressor lncRNAs, such as TSLNC8, TPTEP1, and DILC decrease STAT3 expression. These lncRNAs can affect STAT3 signaling activity through numerous molecular mechanisms, including sponge of microRNAs, transcriptional activation/inhibition, and epigenetic alterations. Numerous studies show that targeting lncRNAs and molecules associated with the STAT3 signaling pathway are promising therapeutic strategies for various cancers. This review highlighted the mechanisms of the upstream lncRNAs of the STAT3 signaling pathway. 

کلیدواژه‌ها

STAT3 Transcription Factor؛ Genetics؛ Oncogenes؛ Tumor Suppressor؛ MicroRNAs

مراجع

Alipoor B., Parvar S. N., Sabati Z., Ghaedi H. and Ghasemi H. (2020) An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance. Mol Biol Rep 47:6357-6374.

 Banerjee K. and Resat H. (2016) Constitutive activation of STAT3 in breast cancer cells: A review. Int J Cancer 138:2570-2578.

Carpenter R. L. and Lo H. W. (2014) STAT3 Target Genes Relevant to Human Cancers. Cancers (Basel) 6:897-925.

Chan J. J. and Tay Y. (2018) Noncoding RNA:RNA Regulatory Networks in Cancer. Int J Mol Sci 19.

Chang S. M. and Hu W. W. (2018) Long non‐coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA‐125b/STAT3 axis. Journal of Cellular Physiology 233:3384-3396.

Cheetham S. W., Gruhl F., Mattick J. S. and Dinger M. E. (2013) Long noncoding RNAs and the genetics of cancer. Br J Cancer 108:2419-2425.

Chen D. and Yu X. (2018) Long noncoding RNA TSLNC8 suppresses cell proliferation and metastasis and promotes cell apoptosis in human glioma. Molecular medicine reports 18:5536-5544.

Chen L., Feng P., Zhu X., He S., Duan J. and Zhou D. (2016a) Long non‐coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells. Journal of cellular and molecular medicine 20:2102-2110.

Chen M. J., Deng J., Chen C., Hu W., Yuan Y. C. and Xia Z. K. (2019a) LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis. Int J Biochem Cell Biol 113:27-36.

 Chen Z., Chen X., Xie R., Huang M., Dong W., Han J., Zhang J., Zhou Q., Li H., Huang J. and Lin T. (2019b) DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression. Mol Ther 27:326-341.

Chen Z. J., Zhang Z., Xie B. B. and Zhang H. Y. (2016b) Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian cancer. Eur Rev Med Pharmacol Sci 20:3373-3377.

Das R., Gregory P. A., Fernandes R. C., Denis I., Wang Q., Townley S. L., Zhao S. G., Hanson A. R., Pickering M. A. and Armstrong H. K. (2017) MicroRNA-194 promotes prostate cancer metastasis by inhibiting SOCS2. Cancer research 77:1021-1034.

de Araujo E. D., Keseru G. M., Gunning P. T. and Moriggl R. (2020) Targeting STAT3 and STAT5 in Cancer. Cancers (Basel) 12.

Dehghan F., Boozarpour S., Torabizadeh Z. and Alijanpour S. (2019) miR-21: a promising biomarker for the early detection of colon cancer. OncoTargets and therapy 12:5601.

Díaz-Beyá M., Brunet S., Nomdedéu J., Pratcorona M., Cordeiro A., Gallardo D., Escoda L., Tormo M., Heras I. and Ribera J. M. (2015) The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature. Oncotarget 6:31613.

Ding H., Liu J., Zou R., Cheng P. and Su Y. (2019) Long non-coding RNA TPTEP1 inhibits hepatocellular carcinoma progression by suppressing STAT3 phosphorylation. J Exp Clin Cancer Res 38:189.

Do H. and Kim W. (2018) Roles of Oncogenic Long Non-coding RNAs in Cancer Development. Genomics Inform 16:e18.

Dong P., Xiong Y., Yue J., Hanley S. J., Kobayashi N., Todo Y. and Watari H. (2018) Long non-coding RNA NEAT1: a novel target for diagnosis and therapy in human tumors. Frontiers in genetics 9:471.

Dong Y., Liang G., Yuan B., Yang C., Gao R. and Zhou X. (2015) MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumor Biology 36:1477-1486.

Esmatabadi M. J. D., Farhangi B., Montazeri M., Monfared H., Sistani R. N. and Sadeghizadeh M. (2017) Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells. Iranian journal of basic medical sciences 20:350.

Fan H., Li J., Wang J. and Hu Z. (2019) Long Non-Coding RNAs (lncRNAs) Tumor-Suppressive Role of lncRNA on Chromosome 8p12 (TSLNC8) Inhibits Tumor Metastasis and Promotes Apoptosis by Regulating Interleukin 6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3)/Hypoxia-Inducible Factor 1-alpha (HIF-1alpha) Signaling Pathway in Non-Small Cell Lung Cancer. Med Sci Monit 25:7624-7633.

Fang X., Zhong G., Wang Y., Lin Z., Lin R. and Yao T. (2020) Low GAS5 expression may predict poor survival and cisplatin resistance in cervical cancer. Cell death & disease 11:1-17.

Fu J. W., Kong Y. and Sun X. (2016) Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer. J Cancer Res Clin Oncol 142:1571-1579.

Ghafouri-Fard S. and Taheri M. (2019) Nuclear enriched abundant transcript 1 (NEAT1): a long non-coding RNA with diverse functions in tumorigenesis. Biomedicine & Pharmacotherapy 111:51-59.

Gu L. Q., Xing X. L., Cai H., Si A. F., Hu X. R., Ma Q. Y., Zheng M. L., Wang R. Y., Li H. Y. and Zhang X. P. (2018) Long non-coding RNA DILC suppresses cell proliferation and metastasis in colorectal cancer. Gene 666:18-26.

Guzel E., Okyay T. M., Yalcinkaya B., Karacaoglu S., Gocmen M. and Akcakuyu M. H. (2020) Tumor suppressor and oncogenic role of long non-coding RNAs in cancer. North Clin Istanb 7:81-86.

 Hamilton M. J., Young M., Jang K., Sauer S., Neang V. E., King A. T., Girke T. and Martinez E. (2020) HOTAIRM1 lncRNA is downregulated in clear cell renal cell carcinoma and inhibits the hypoxia pathway. Cancer letters 472:50-58.

 He C., Jiang B., Ma J. and Li Q. (2016) Aberrant NEAT1 expression is associated with clinical outcome in high grade glioma patients. APMIS 124:169-174.

 Hinohara K., Kobayashi S., Kanauchi H., Shimizu S., Nishioka K., Tsuji E., Tada K., Umezawa K., Mori M., Ogawa T., Inoue J., Tojo A. and Gotoh N. (2012) ErbB receptor tyrosine kinase/NF-kappaB signaling controls mammosphere formation in human breast cancer. Proc Natl Acad Sci U S A 109:6584-6589.

 Hu C., Liu S., Han M., Wang Y. and Xu C. (2018) RETRACTED: Knockdown of lncRNA XIST inhibits retinoblastoma progression by modulating the miR-124/STAT3 axis. Biomed Pharmacother 107:547-554.

 Johnson D. E., O'Keefe R. A. and Grandis J. R. (2018) Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 15:234-248.

Kagoya Y., Yoshimi A., Kataoka K., Nakagawa M., Kumano K., Arai S., Kobayashi H., Saito T., Iwakura Y. and Kurokawa M. (2014) Positive feedback between NF-kappaB and TNF-alpha promotes leukemia-initiating cell capacity. J Clin Invest 124:528-542.

Kim C. Y., Oh J. H., Lee J.-Y. and Kim M. H. (2020) The LncRNA HOTAIRM1 promotes tamoxifen resistance by mediating HOXA1 expression in ER+ Breast Cancer Cells. Journal of Cancer 11:3416.

Kretz M., Webster D. E., Flockhart R. J., Lee C. S., Zehnder A., Lopez-Pajares V., Qu K., Zheng G. X., Chow J. and Kim G. E. (2012) Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes & development 26:338-343.

Kulczynska K. and Siatecka M. (2016) A regulatory function of long non-coding RNAs in red blood cell development. Acta Biochim Pol 63:675-680.

Lashkarboloki M., Boozarpour S., Jorjani E., Sabouri H. and Fahimi M. (2020) Association Study of miR-124-a-3 Gene rs34059726 Polymorphism with Prostate Cancer in Gonbad Kavous.

Li J. P., Xiang Y., Fan L. J., Yao A., Li H. and Liao X. H. (2019a) Long noncoding RNA H19 competitively binds miR-93-5p to regulate STAT3 expression in breast cancer. J Cell Biochem 120:3137-3148.

Li Q., Dong C., Cui J., Wang Y. and Hong X. (2018a) Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. Journal of Experimental & Clinical Cancer Research 37:1-15.

Li Q. G., Xu X. Q., Zhou D. Y., Jia Z. B., Yu B. F., Xu F. G. and Zhang L. (2019b) Long non-coding RNA DILC as a potentially useful biomarker for the diagnosis and prognosis of colorectal cancer. Eur Rev Med Pharmacol Sci 23:3320-3325.

Li S., Mei Z., Hu H. B. and Zhang X. (2018b) The lncRNA MALAT1 contributes to non‐small cell lung cancer development via modulating miR‐124/STAT3 axis. Journal of Cellular Physiology 233:6679-6688.

Li X., Pang L., Yang Z., Liu J., Li W. and Wang D. (2019c) LncRNA HOTAIRM1/HOXA1 axis promotes cell proliferation, migration and invasion in endometrial cancer. OncoTargets and therapy 12:10997.

Li X., Yu M. and Yang C. (2020) YY1-mediated overexpression of long noncoding RNA MCM3AP-AS1 accelerates angiogenesis and progression in lung cancer by targeting miR-340-5p/KPNA4 axis. J Cell Biochem 121:2258-2267.

Li Z., Qin X., Bian W., Li Y., Shan B., Yao Z. and Li S. (2019d) Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis. J Exp Clin Cancer Res 38:477.

Liang J., Liang L., Ouyang K., Li Z. and Yi X. (2017) MALAT 1 induces tongue cancer cells' EMT and inhibits apoptosis through Wnt/β‐catenin signaling pathway. Journal of oral pathology & medicine 46:98-105.

Liang M., Jia J., Chen L., Wei B., Guan Q., Ding Z., Yu J., Pang R. and He G. (2019) LncRNA MCM3AP-AS1 promotes proliferation and invasion through regulating miR-211-5p/SPARC axis in papillary thyroid cancer. Endocrine 65:318-326.

Liang Q., Ding J., Xu R., Xu Z. and Zheng S. (2010) The novel human endogenous retrovirus-related gene, psiTPTE22-HERV, is silenced by DNA methylation in cancers. Int J Cancer 127:1833-1843.

 Lin W. H., Chang Y. W., Hong M. X., Hsu T. C., Lee K. C., Lin C. and Lee J. L. (2021) STAT3 phosphorylation at Ser727 and Tyr705 differentially regulates the EMT-MET switch and cancer metastasis. Oncogene 40:791-805.

Liu L., Liu L. and Lu S. (2019) lncRNA H19 promotes viability and epithelial-mesenchymal transition of lung adenocarcinoma cells by targeting miR-29b-3p and modifying STAT3. Int J Oncol 54:929-941.

Liu S., Yan G., Zhang J. and Yu L. (2018) Knockdown of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) inhibits proliferation, migration, and invasion and promotes apoptosis by targeting miR-124 in retinoblastoma. Oncology research 26:581.

50- Lu Q. c., Rui Z. h., Guo Z. l., Xie W., Shan S. and Ren T. (2018) Lnc RNA‐DANCR contributes to lung adenocarcinoma progression by sponging miR‐496 to modulate mTOR expression. Journal of cellular and molecular medicine 22:1527-1537.

Luo Z. and Cao P. (2019) Long noncoding RNA PVT1 promotes hepatoblastoma cell proliferation through activating STAT3. Cancer Manag Res 11:8517-8527.

Ma Q. Y., Li S. Y., Li X. Z., Zhou T. F., Zhao Y. F., Liu F. L., Yu X. N., Lin J., Chen F. Y., Cao J., Xi H. J. and Li H. Y. (2019) Long non-coding RNA DILC suppresses bladder cancer cells progression. Gene 710:193-201.

Mohankumar K. M., Perry J. K., Kannan N., Kohno K., Gluckman P. D., Emerald B. S. and Lobie P. E. (2008) Transcriptional activation of signal transducer and activator of transcription (STAT) 3 and STAT5B partially mediate homeobox A1-stimulated oncogenic transformation of the immortalized human mammary epithelial cell. Endocrinology 149:2219-2229.

Onagoruwa O. T., Pal G., Ochu C. and Ogunwobi O. O. (2020) Oncogenic Role of PVT1 and Therapeutic Implications. Front Oncol 10:17.

Poursheikhani A., Abbaszadegan M. R., Nokhandani N. and Kerachian M. A. (2020) Integration analysis of long non-coding RNA (lncRNA) role in tumorigenesis of colon adenocarcinoma. BMC Med Genomics 13:108.

 Prensner J. R. and Chinnaiyan A. M. (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1:391-407.

Qin J.-J., Yan L., Zhang J. and Zhang W.-D. (2019a) STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. Journal of Experimental & Clinical Cancer Research 38:1-16.

 Qin J. J., Yan L., Zhang J. and Zhang W. D. (2019b) STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J Exp Clin Cancer Res 38:195.

 Reymond A., Camargo A. A., Deutsch S., Stevenson B. J., Parmigiani R. B., Ucla C., Bettoni F., Rossier C., Lyle R. and Guipponi M. (2002) Nineteen additional unpredicted transcripts from human chromosome 21. Genomics 79:824-832.

Saliani M., Mirzaiebadizi A., Javadmanesh A., Siavoshi A. and Ahmadian M. R. (2021) KRAS-related long noncoding RNAs in human cancers. Cancer Gene Ther.

 Sana J., Faltejskova P., Svoboda M. and Slaby O. (2012) Novel classes of non-coding RNAs and cancer. J Transl Med 10:103.

 Sánchez Y. and Huarte M. (2013) Long non-coding RNAs: challenges for diagnosis and therapies. Nucleic acid therapeutics 23:15-20.

 Savari B., Boozarpour S., Tahmasebi-Birgani M., Sabouri H. and Hosseini S. M. (2020) Overexpression of microRNA-21 in the Serum of Breast Cancer Patients. MicroRNA 9:58-63.

 Schroeder A., Herrmann A., Cherryholmes G., Kowolik C., Buettner R., Pal S., Yu H., Müller-Newen G. and Jove R. (2014) Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer research 74:1227-1237.

Segatto I., Baldassarre G. and Belletti B. (2018) STAT3 in breast cancer onset and progression: a matter of time and context. International journal of molecular sciences 19:2818.

 Shang R., Wang M., Dai B., Du J., Wang J., Liu Z., Qu S., Yang X., Liu J., Xia C., Wang L., Wang D. and Li Y. (2020) Long noncoding RNA SLC2A1-AS1 regulates aerobic glycolysis and progression in hepatocellular carcinoma via inhibiting the STAT3/FOXM1/GLUT1 pathway. Mol Oncol 14:1381-1396.

 Shi X., Sun M., Liu H., Yao Y. and Song Y. (2013) Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett 339:159-166.

 Shin V. Y., Chen J., Cheuk I. W., Siu M. T., Ho C. W., Wang X., Jin H. and Kwong A. (2019) Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death Dis 10:270.

Sun Y. and Ma L. (2019) New insights into long non-coding RNA MALAT1 in cancer and metastasis. Cancers 11:216.

Tan H. Y., Wang C., Liu G. and Zhou X. (2019) Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3. J Cell Biochem 120:4827-4836.

van Heesch S., van Iterson M., Jacobi J., Boymans S., Essers P. B., de Bruijn E., Hao W., MacInnes A. W., Cuppen E. and Simonis M. (2014) Extensive localization of long noncoding RNAs to the cytosol and mono-and polyribosomal complexes. Genome biology 15:1-12.

Wang J., Sun J. and Yang F. (2020a) The role of long non-coding RNA H19 in breast cancer. Oncol Lett 19:7-16.

Wang L., Zhang Y. and Xin X. (2020b) Long non-coding RNA MALAT1 aggravates human retinoblastoma by sponging miR-20b-5p to upregulate STAT3. Pathology-Research and Practice 216:152977.

Wang X., Sun W., Shen W., Xia M., Chen C., Xiang D., Ning B., Cui X., Li H., Li X., Ding J. and Wang H. (2016) Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. J Hepatol 64:1283-1294.

Wang Y., Yang L., Chen T., Liu X., Guo Y., Zhu Q., Tong X., Yang W., Xu Q., Huang D. and Tu K. (2019) A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer 18:28.

Xia H., Liu Y., Wang Z., Zhang W., Qi M., Qi B. and Jiang X. (2020) Long noncoding RNA HOTAIRM1 maintains tumorigenicity of glioblastoma stem-like cells through regulation of hox gene expression. Neurotherapeutics 17:754-764.

XianGuo C., ZongYao H., Jun Z., Song F., GuangYue L., LiGang Z., KaiPing Z., YangYang Z. and ChaoZhao L. (2016) Promoting progression and clinicopathological significance of NEAT1 over-expression in bladder cancer. Oncotarget 5.

 Xie P., Li X., Chen R., Liu Y., Liu D., Liu W., Cui G. and Xu J. (2021) Upregulation of HOTAIRM1 increases migration and invasion by glioblastoma cells. Aging (Albany NY) 13:2348.

Yang C., Zheng J., Xue Y., Yu H., Liu X., Ma J., Liu L., Wang P., Li Z., Cai H. and Liu Y. (2017) The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 Axis Regulating Glioblastoma Angiogenesis. Front Mol Neurosci 10:437.

Yang J., Chatterjee-Kishore M., Staugaitis S. M., Nguyen H., Schlessinger K., Levy D. E. and Stark G. R. (2005) Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res 65:939-947.

Yang X., Xie Z., Lei X. and Gan R. (2020) Long non‑coding RNA GAS5 in human cancer. Oncology letters 20:2587-2594.

Yao T., Lu R., Zhang J., Fang X., Fan L., Huang C., Lin R. and Lin Z. (2019) Growth arrest‐specific 5 attenuates cisplatin‐induced apoptosis in cervical cancer by regulating STAT3 signaling via miR‐21. Journal of Cellular Physiology 234:9605-9615.

Yu H., Xu Q., Liu F., Ye X., Wang J. and Meng X. (2015) Identification and validation of long noncoding RNA biomarkers in human non–small-cell lung carcinomas. Journal of thoracic oncology 10:645-654.

 Yuan J., Ji H., Xiao F., Lin Z., Zhao X., Wang Z., Zhao J. and Lu J. (2017) MicroRNA-340 inhibits the proliferation and invasion of hepatocellular carcinoma cells by targeting JAK1. Biochem Biophys Res Commun 483:578-584.

Yuan S. x., Wang J., Yang F., Tao Q. f., Zhang J., Wang L. l., Yang Y., Liu H., Wang Z. g. and Xu Q. g. (2016a) Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1. Hepatology 63:499-511.

 Yuan Y., Cai T., Xia X., Zhang R., Chiba P. and Cai Y. (2016b) Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer. Drug Deliv 23:3350-3357.

 Zhang H., Luo C. and Zhang G. (2019a) LncRNA MCM3AP-AS1 Regulates Epidermal Growth Factor Receptor and Autophagy to Promote Hepatocellular Carcinoma Metastasis by Interacting with miR-455. DNA Cell Biol 38:857-864.

 Zhang J., Li Z., Liu L., Wang Q., Li S., Chen D., Hu Z., Yu T., Ding J., Li J., Yao M., Huang S., Zhao Y. and He X. (2018a) Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology 67:171-187.

 Zhang L., Liu B., Deng Q. and Li J. (2020) LncRNA BRE-AS1 acts as a tumor suppressor factor in bladde r cancer via mediating STAT3. Eur. Rev. Med. Pharmacol. Sci 24:5320-5328.

 Zhang T., Hu H., Yan G., Wu T., Liu S., Chen W., Ning Y. and Lu Z. (2019b) Long Non-Coding RNA and Breast Cancer. Technol Cancer Res Treat 18:1533033819843889.

 Zhang X., Lian Z., Padden C., Gerstein M. B., Rozowsky J., Snyder M., Gingeras T. R., Kapranov P., Weissman S. M. and Newburger P. E. (2009) A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113:2526-2534.

Zhang X., Yang J., Bian Z., Shi D. and Cao Z. (2019c) Long noncoding RNA DANCR promotes nasopharyngeal carcinoma progression by interacting with STAT3, enhancing IL-6/JAK1/STAT3 signaling. Biomed Pharmacother 113:108713.

 Zhang X. N., Zhou J. and Lu X. J. (2018b) The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development by sponging miR-485 and enhancing the expression of the STAT3. J Cell Physiol 233:6733-6741.

 Zhao G., Su Z., Song D., Mao Y. and Mao X. (2016) The long noncoding RNA MALAT 1 regulates the lipopolysaccharide‐induced inflammatory response through its interaction with NF‐κB. FEBS letters 590:2884-2895.

 Zhao J., Wu J., Qin Y., Zhang W., Huang G. and Qin L. (2020) LncRNA PVT1 induces aggressive vasculogenic mimicry formation through activating the STAT3/Slug axis and epithelial-to-mesenchymal transition in gastric cancer. Cell Oncol (Dordr) 43:863-876.

 Zhong Z., Wen Z. and Darnell J. E., Jr. (1994) Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95-98.

 Zhu Y., Shi L., Zhou C., Wang Z., Yu T., Zhou J. and Yang Y. (2019) Long non-coding RNA MCM3AP-AS1 inhibits cell viability and promotes apoptosis in ovarian cancer cells by targeting miR-28-5p. Int. J. Clin. Exp. Med 12:2939-2951.