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Long non-coding RNAs and cancer mechanisms: Immune cells and inflammatory cytokines in the tumor microenvironment

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Abstract

Chronic inflammation and immune response are two central hallmarks of the tumor microenvironment (TME), teeming with immune cells and inflammatory cytokines that promote tumor progression. Intriguingly, there is mutual regulation between immune cells and cytokines. Indeed, the differentiation and function of immune cells depend on cytokines secreted from tumor cells, whereas immune activation affects the dynamics of cytokines, reshaping the TME together. Long non-coding RNAs (lncRNAs) as a blooming molecule are virtually involved in physiology and pathology events, especially TME. Notably, the regulatory loop between lncRNAs and cytokines or immune activation plays a vital role in tumor growth. Thus, this review concentrates on the interaction between lncRNAs and immune cells. It puts special attention to the intertwist between lncRNAs and cytokines or immune cells, providing a theoretical basis for lncRNAs as a potential biomarker and therapeutic tumor target.

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References

  1. Balkwill F, Mantovani A. Inflammation and cancer: back to virchow? Lancet. 2001;357(9255):539–45.

    Article  CAS  PubMed  Google Scholar 

  2. Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity. 2019;51(1):27–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bu P, Wang L, Chen KY, Srinivasan T, Murthy PK, Tung KL, Varanko AK, Chen HJ, Ai Y, King S, et al. A miR-34a-numb feedforward loop triggered by inflammation regulates asymmetric stem cell division in intestine and colon cancer. Cell Stem Cell. 2016;18(2):189–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Katoh H, Wang D, Daikoku T, Sun H, Dey SK, Dubois RN. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell. 2013;24(5):631–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Stone ML, Beatty GL. Cellular determinants and therapeutic implications of inflammation in pancreatic cancer. Pharmacol Ther. 2019;201:202–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ritter B, Greten FR. Modulating inflammation for cancer therapy. J Exp Med. 2019;216(6):1234–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhu J, Fu H, Wu Y, Zheng X. Function of lncRNAs and approaches to lncRNA-protein interactions. Sci China Life Sci. 2013;56(10):876–85.

    Article  CAS  PubMed  Google Scholar 

  8. Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. J CELL BIOL. 2021;220(2):e202009045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu W, Ma R, Yuan Y. Post-transcriptional regulation of genes related to biological behaviors of gastric cancer by long noncoding RNAs and MicroRNAs. J Cancer. 2017;8(19):4141–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, Li J, Li F, Tan HB. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett. 2020;470:126–33.

    Article  CAS  PubMed  Google Scholar 

  11. Padoan A, Plebani M, Basso D. Inflammation and pancreatic cancer: focus on metabolism, cytokines, and immunity. Int J Mol Sci. 2019;20(3):676.

    Article  CAS  PubMed Central  Google Scholar 

  12. Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells. Nat Rev Cancer. 2013;13(10):739–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Weber R, Groth C, Lasser S, Arkhypov I, Petrova V, Altevogt P, Utikal J. Umansky V (2021) IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy. Cell Immunol. 2021;359:104254.

    Article  CAS  PubMed  Google Scholar 

  15. Zheng Y, Tian X, Wang T, Xia X, Cao F, Tian J, Xu P, Ma J, Xu H, Wang S. Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. Mol Cancer. 2019;18(1):61.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tian X, Zheng Y, Yin K, Ma J, Tian J, Zhang Y, Mao L, Xu H, Wang S. LncRNA AK036396 inhibits maturation and accelerates immunosuppression of polymorphonuclear myeloid-derived suppressor cells by enhancing the stability of ficolin B. Cancer Immunol Res. 2020;8(4):565–77.

    Article  CAS  PubMed  Google Scholar 

  17. Gao Y, Wang T, Li Y, Zhang Y, Yang R. Lnc-chop promotes immunosuppressive function of myeloid-derived suppressor cells in tumor and inflammatory environments. J Immunol. 2018;200(8):2603–14.

    Article  CAS  PubMed  Google Scholar 

  18. Tian X, Ma J, Wang T, Tian J, Zheng Y, Peng R, Wang Y, Zhang Y, Mao L, Xu H, et al. Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer. BMC Cancer. 2018;18(1):660.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Zhou Q, Tang X, Tian X, Tian J, Zhang Y, Ma J, Xu H, Wang S. LncRNA MALAT1 negatively regulates MDSCs in patients with lung cancer. J Cancer. 2018;9(14):2436–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Tian X, Ma J, Wang T, Tian J, Zhang Y, Mao L, Xu H, Wang S. Long non-coding RNA HOXA transcript antisense RNA myeloid-specific 1-HOXA1 axis downregulates the immunosuppressive activity of myeloid-derived suppressor cells in lung cancer. Front Immunol. 2018;9:473.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Cervantes J, Michael M, Hong BY, Springer A, Guo H, Mendoza B, Zeng M, Sundin O, McCallum R. Investigation of oral, gastric, and duodenal microbiota in patients with upper gastrointestinal symptoms. J Investig Med. 2020;69(4):870–7.

    Article  Google Scholar 

  22. Erin N, Grahovac J, Brozovic A, Efferth T. Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resist Updat. 2020;53:100715.

    Article  PubMed  Google Scholar 

  23. Chen C, He W, Huang J, Wang B, Li H, Cai Q, Su F, Bi J, Liu H, Zhang B, et al. LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment. Nat Commun. 2018;9(1):3826.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Fujisaka Y, Iwata T, Tamai K, Nakamura M, Mochizuki M, Shibuya R, Yamaguchi K, Shimosegawa T, Satoh K. Long non-coding RNA HOTAIR up-regulates chemokine (C-C motif) ligand 2 and promotes proliferation of macrophages and myeloid-derived suppressor cells in hepatocellular carcinoma cell lines. Oncol Lett. 2018;15(1):509–14.

    PubMed  Google Scholar 

  25. Hsieh CC, Wang CH. Aspirin disrupts the crosstalk of angiogenic and inflammatory cytokines between 4T1 breast cancer cells and macrophages. Mediators Inflamm. 2018;2018:6380643.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Funes SC, Rios M, Escobar-Vera J, Kalergis AM. Implications of macrophage polarization in autoimmunity. Immunology. 2018;154(2):186–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang LX, Zhang SX, Wu HJ, Rong XL, Guo J. M2b macrophage polarization and its roles in diseases. J Leukoc Biol. 2019;106(2):345–58.

    Article  CAS  PubMed  Google Scholar 

  28. Tao S, Chen Q, Lin C, Dong H. Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway. J Exp Clin Cancer Res. 2020;39(1):191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tu J, Wu F, Chen L, Zheng L, Yang Y, Ying X, Song J, Chen C, Hu X, Zhao Z, et al. Long non-coding RNA PCAT6 induces M2 polarization of macrophages in cholangiocarcinoma via modulating miR-326 and RhoA-ROCK signaling pathway. Front Oncol. 2020;10:605877.

    Article  PubMed  Google Scholar 

  30. Dong F, Ruan S, Wang J, Xia Y, Le K, Xiao X, Hu T, Wang Q. M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2. Cell Death Dis. 2020;11(9):728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sawa-Wejksza K, Kandefer-Szerszen M. Tumor-associated macrophages as target for antitumor Therapy. Arch Immunol Ther Exp (Warsz). 2018;66(2):97–111.

    Article  CAS  Google Scholar 

  32. Zhao Y, Yu Z, Ma R, Zhang Y, Zhao L, Yan Y, Lv X, Zhang L, Su P, Bi J, et al. lncRNA-Xist/miR-101-3p/KLF6/C/EBPalpha axis promotes TAM polarization to regulate cancer cell proliferation and migration. Mol Ther Nucleic Acids. 2021;23:536–51.

    Article  CAS  PubMed  Google Scholar 

  33. Luo HL, Luo T, Liu JJ, Wu FX, Bai T, Ou C, Chen J, Li LQ, Zhong JH. Macrophage polarization-associated lnc-Ma301 interacts with caprin-1 to inhibit hepatocellular carcinoma metastasis through the Akt/Erk1 pathway. Cancer Cell Int. 2021;21(1):422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Maibach F, Sadozai H, Seyed JS, Hunger RE, Schenk M. Tumor-infiltrating lymphocytes and their prognostic value in cutaneous melanoma. Front Immunol. 2020;11:2105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Krishna S, Lowery FJ, Copeland AR, Bahadiroglu E, Mukherjee R, Jia L, Anibal JT, Sachs A, Adebola SO, Gurusamy D, et al. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science. 2020;370(6522):1328–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Paijens ST, Vledder A, de Bruyn M, Nijman HW. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol. 2021;18(4):842–59.

    Article  CAS  PubMed  Google Scholar 

  37. Hall M, Liu H, Malafa M, Centeno B, Hodul PJ, Pimiento J, Pilon-Thomas S, Sarnaik AA. Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors. J Immunother Cancer. 2016;4:61.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sun CC, Zhu W, Li SJ, Hu W, Zhang J, Zhuo Y, Zhang H, Wang J, Zhang Y, Huang SX, et al. FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1alpha pathway. Genome Med. 2020;12(1):77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang X, Zhang Y, Zheng J, Yao C, Lu X. LncRNA UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on anaplastic thyroid carcinoma via miR-148a/PD-L1 pathway. Cancer Immunol Immunother. 2021;70(8):2235–45.

    Article  CAS  PubMed  Google Scholar 

  40. Lin ZB, Long P, Zhao Z, Zhang YR, Chu XD, Zhao XX, Ding H, Huan SW, Pan YL, Pan JH. Long noncoding RNA KCNQ1OT1 is a prognostic biomarker and mediates CD8(+) T cell exhaustion by regulating CD155 expression in colorectal cancer. Int J Biol Sci. 2021;17(7):1757–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang Y, Dong X, Wang Y, Wang L, Han G, Jin L, Fan Y, Xu G, Yuan D, Zheng J, et al. Overexpression of LncRNA BM466146 Predicts Better Prognosis of Breast Cancer. Front Oncol. 2020;10:628757.

    Article  PubMed  Google Scholar 

  42. Li G, Kryczek I, Nam J, Li X, Li S, Li J, Wei S, Grove S, Vatan L, Zhou J, et al. LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy. Nat Cell Biol. 2021;23(5):526–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Brajic A, Franckaert D, Burton O, Bornschein S, Calvanese AL, Demeyer S, Cools J, Dooley J, Schlenner S, Liston A. The long non-coding RNA flatr anticipates Foxp3 expression in regulatory T cells. Front Immunol. 1989;2018:9.

    Google Scholar 

  45. Zemmour D, Pratama A, Loughhead SM, Mathis D, Benoist C. Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity. Proc Natl Acad Sci U S A. 2017;114(17):E3472–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yu Z, Zhao H, Feng X, Li H, Qiu C, Yi X, Tang H, Zhang J. Long non-coding RNA FENDRR Acts as a miR-423-5p sponge to suppress the treg-mediated immune Escape of hepatocellular carcinoma cells. Mol Ther Nucleic Acids. 2019;17:516–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Xiaoli T, Wenting W, Meixiang Z, Chunlei Z, Chengxia H. Long noncoding RNA RP11–357H14.17 plays an oncogene role in gastric cancer by activating ATF2 signaling and enhancing treg cells. Biomed Res Int. 2021;2021:6635936.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Wang J, Huang F, Shi Y, Zhang Q, Xu S, Yao Y, Jiang R. RP11–323N125 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription. Gastric Cancer. 2021;24(1):85–102.

    Article  CAS  PubMed  Google Scholar 

  49. Pyfrom SC, Quinn CC, Dorando HK, Luo H, Payton JE. BCALM (AC099524.1) is a human B lymphocyte-specific long noncoding RNA that modulates B cell receptor-mediated calcium signaling. J Immunol. 2020;205(3):595–607.

    Article  CAS  PubMed  Google Scholar 

  50. Zhou M, Zhang Z, Bao S, Hou P, Yan C, Su J, Sun J. Computational recognition of lncRNA signature of tumor-infiltrating B lymphocytes with potential implications in prognosis and immunotherapy of bladder cancer. Brief Bioinform. 2021. https://doi.org/10.1093/bib/bbaa047.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, et al. Tissue determinants of human nk cell development, function, and residence. Cell. 2020;180(4):749–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Stein N, Berhani O, Schmiedel D, Duev-Cohen A, Seidel E, Kol I, Tsukerman P, Hecht M, Reches A, Gamliel M, et al. IFNG-AS1 enhances interferon gamma production in human natural killer cells. iScience. 2019;11:466–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wei MF, Gu ZS, Zheng LL, Zhao MX, Wang XJ. Long non-coding RNA GAS5 promotes natural killer cell cytotoxicity against gastric cancer by regulating miR-18a. Neoplasma. 2020;67(5):1085–93.

    Article  CAS  PubMed  Google Scholar 

  54. Fang P, Xiang L, Chen W, Li S, Huang S, Li J, Zhuge L, Jin L, Feng W, Chen Y, et al. LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3. Innate Immun. 2019;25(2):99–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang Y, Li X, Zhang J, Liang H. Natural killer T cell cytotoxic activity in cervical cancer is facilitated by the LINC00240/microRNA-124-3p/STAT3/MICA axis. Cancer Lett. 2020;474:63–73.

    Article  CAS  PubMed  Google Scholar 

  56. Qin X, Zhou M, Lv H, Mao X, Li X, Guo H, Li L, Xing H. Long noncoding RNA LINC00657 inhibits cervical cancer development by sponging miR-20a-5p and targeting RUNX3. Cancer Lett. 2021;498:130–41.

    Article  CAS  PubMed  Google Scholar 

  57. Sun J, Yu J, Li H, Yang L, Wei F, Yu W, Liu J, Ren X. Up-regulated expression of indoleamine 2, 3-dioxygenase in CHO cells induces apoptosis of competent T cells and increases proportion of Treg cells. J Exp Clin Cancer Res. 2011;30:82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ozga AJ, Chow MT, Luster AD. Chemokines and the immune response to cancer. Immunity. 2021;54(5):859–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Palmieri B, Vadala’ M, Palmieri L. Immune memory: an evolutionary perspective. Hum Vaccin Immunother. 2021;17(6):1604–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wolf J, Rose-John S, Garbers C. Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine. 2014;70(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  61. Hossain DM, Panda AK, Manna A, Mohanty S, Bhattacharjee P, Bhattacharyya S, Saha T, Chakraborty S, Kar RK, Das T, et al. FoxP3 acts as a cotranscription factor with STAT3 in tumor-induced regulatory T cells. Immunity. 2013;39(6):1057–69.

    Article  CAS  PubMed  Google Scholar 

  62. Sun B, Han Y, Cai H, Huang H, Xuan Y. Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis. Cell Oncol (Dordr). 2021;44(1):179–92.

    Article  CAS  Google Scholar 

  63. Al AR, Sheth S, Alanisi E, Borse V, Mukherjea D, Rybak LP. Ramkumar V (2017) Tonic suppression of PCAT29 by the IL-6 signaling pathway in prostate cancer: Reversal by resveratrol. PLoS ONE. 2017;12(5):e177198.

    Google Scholar 

  64. Wu S, Liu B, Zhang Y, Hong R, Liu S, Xiang T, Tao T, Cai J, Wu J, Li M, et al. Long non-coding RNA LEISA promotes progression of lung adenocarcinoma via enhancing interaction between STAT3 and IL-6 promoter. Oncogene. 2021;40(19):3449–59.

    Article  CAS  PubMed  Google Scholar 

  65. Nakano Y, Isobe K, Kobayashi H, Kaburaki K, Isshiki T, Sakamoto S, Takai Y, Tochigi N, Mikami T, Iyoda A, et al. Clinical importance of long noncoding RNA LINC00460 expression in EGFRmutant lung adenocarcinoma. Int J Oncol. 2020;56(1):243–57.

    CAS  PubMed  Google Scholar 

  66. Li MX, Wang HY, Yuan CH, Ma ZL, Jiang B, Li L, Zhang L, Xiu DR. KLHDC7B-DT aggravates pancreatic ductal adenocarcinoma development via inducing cross-talk between cancer cells and macrophages. Clin Sci (Lond). 2021;135(4):629–49.

    Article  CAS  Google Scholar 

  67. LeBleu VS, Kalluri R. A peek into cancer-associated fibroblasts: origins, functions and translational impact. Dis Model Mech. 2018. https://doi.org/10.1242/dmm.029447.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Wang Z, Wang X, Zhang T, Su L, Liu B, Zhu Z, Li C. LncRNA MALAT1 promotes gastric cancer progression via inhibiting autophagic flux and inducing fibroblast activation. Cell Death Dis. 2021;12(4):368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, Perez-Gracia JL, Rodriguez-Ruiz ME, Ponz-Sarvise M, Castanon E, Melero I. Cytokines in clinical cancer immunotherapy. Br J Cancer. 2019;120(1):6–15.

    Article  CAS  PubMed  Google Scholar 

  70. Li L, Yu R, Cai T, Chen Z, Lan M, Zou T, Wang B, Wang Q, Zhao Y, Cai Y. Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment. Int Immunopharmacol. 2020;88:106939.

    Article  CAS  PubMed  Google Scholar 

  71. Luo J, Chen XQ, Li P. The role of TGF-beta and its receptors in gastrointestinal cancers. Transl Oncol. 2019;12(3):475–84.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Meulmeester E, Ten DP. The dynamic roles of TGF-beta in cancer. J Pathol. 2011;223(2):205–18.

    Article  CAS  PubMed  Google Scholar 

  73. Liang J, Liao J, Liu T, Wang Y, Wen J, Cai N, Huang Z, Xu W, Li G, Ding Z, et al. Comprehensive analysis of TGF-beta-induced mRNAs and ncRNAs in hepatocellular carcinoma. Aging (Albany NY). 2020;12(19):19399–420.

    Article  CAS  Google Scholar 

  74. Zheng C, Li R, Zheng S, Fang H, Xu M, Zhong L. LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-beta/SMAD Signaling Pathway and Upregulating SSH2 Expression. Front Mol Biosci. 2021;8:697773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wu N, Jiang M, Liu H, Chu Y, Wang D, Cao J, Wang Z, Xie X, Han Y, Xu B. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-beta/SMAD2/3 signaling pathway. Cell Death Differ. 2021;28(1):219–32.

    Article  CAS  PubMed  Google Scholar 

  76. Wang Y, Yang L, Dong X, Yang X, Zhang X, Liu Z, Zhao X, Wen T. Overexpression of NNT-AS1 activates TGF-beta signaling to decrease tumor CD4 lymphocyte infiltration in hepatocellular carcinoma. Biomed Res Int. 2020;2020:8216541.

    PubMed  PubMed Central  Google Scholar 

  77. Wang H, Li H, Jiang Q, Dong X, Li S, Cheng S, Shi J, Liu L, Qian Z, Dong J. HOTAIRM1 promotes malignant progression of transformed fibroblasts in glioma stem-like cells remodeled microenvironment via regulating miR-133b-3p/TGFbeta axis. Front Oncol. 2021;11:603128.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975;72(9):3666–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Young TM, Reyes C, Pasnikowski E, Castanaro C, Wong C, Decker CE, Chiu J, Song H, Wei Y, Bai Y, et al. Autophagy protects tumors from T cell-mediated cytotoxicity via inhibition of TNFalpha-induced apoptosis. Sci Immunol. 2020. https://doi.org/10.1126/sciimmunol.abb9561.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Benoot T, Piccioni E, De Ridder K, Goyvaerts C. TNFalpha and immune checkpoint inhibition: friend or foe for lung cancer? Int J Mol Sci. 2021;22(16):8691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cruceriu D, Baldasici O, Balacescu O, Berindan-Neagoe I. The dual role of tumor necrosis factor-alpha (TNF-alpha) in breast cancer: molecular insights and therapeutic approaches. Cell Oncol (Dordr). 2020;43(1):1–18.

    Article  CAS  Google Scholar 

  82. Montfort A, Dufau C, Colacios C, Andrieu-Abadie N, Levade T, Filleron T, Delord JP, Ayyoub M, Meyer N, Segui B. Anti-TNF, a magic bullet in cancer immunotherapy? J Immunother Cancer. 2019;7(1):303.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Feng Y, Ma J, Fan H, Liu M, Zhu Y, Li Y, Tang H. TNF-alpha-induced lncRNA LOC105374902 promotes the malignant behavior of cervical cancer cells by acting as a sponge of miR-1285-3p. Biochem Biophys Res Commun. 2019;513(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  84. Xu B, Jin X, Yang T, Zhang Y, Liu S, Wu L, Ying H, Wang Z. Up-regulated lncRNA THRIL/TNF-alpha signals promote cell growth and predict poor clinical outcomes of osteosarcoma. Onco Targets Ther. 2020;13:119–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ma W, Chen X, Wu X, Li J, Mei C, Jing W, Teng L, Tu H, Jiang X, Wang G, et al. Long noncoding RNA SPRY4-IT1 promotes proliferation and metastasis of hepatocellular carcinoma via mediating TNF signaling pathway. J Cell Physiol. 2020;235(11):7849–62.

    Article  CAS  PubMed  Google Scholar 

  86. Guo W, Li J, Huang H, Fu F, Lin Y, Wang C. LncRNA PCIR is an oncogenic driver via strengthen the binding of TAB3 and PABPC4 in triple negative breast cancer. Front Oncol. 2021;11:630300.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118.

    Article  CAS  PubMed  Google Scholar 

  88. Li Y, Song S, Pizzi MP, Han G, Scott AW, Jin J, Xu Y, Wang Y, Huo L, Ma L, et al. LncRNA PVT1 is a poor prognosticator and can be targeted by PVT1 antisense oligos in gastric adenocarcinoma. Cancers (Basel). 2020;12(10):2995.

    Article  CAS  Google Scholar 

  89. Hao Q, Wang P, Dutta P, Chung S, Li Q, Wang K, Li J, Cao W, Deng W, Geng Q, et al. Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA. Cell Death Dis. 2020;11(12):1052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Stackhouse CT, Gillespie GY, Willey CD. Exploring the roles of lncRNAs in GBM pathophysiology and their therapeutic potential. Cells-Basel. 2020;9(11):2369.

    Article  CAS  Google Scholar 

  91. Ming H, Li B, Zhou L, Goel A, Huang C. Long non-coding RNAs and cancer metastasis: molecular basis and therapeutic implications. Biochim Biophys Acta Rev Cancer. 2021;1875:188519.

    Article  CAS  PubMed  Google Scholar 

  92. Chen BW, Zhou Y, Wei T, Wen L, Zhang YB, Shen SC, Zhang J, Ma T, Chen W, Ni L, et al. lncRNA-POIR promotes epithelial-mesenchymal transition and suppresses sorafenib sensitivity simultaneously in hepatocellular carcinoma by sponging miR-182-5p. J Cell Biochem. 2021;122(1):130–42.

    Article  CAS  PubMed  Google Scholar 

  93. Zhen S, Li X. Application of CRISPR-Cas9 for long noncoding RNA genes in cancer research. Hum Gene Ther. 2019;30(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  94. Zhang Z, Chen J, Zhu Z, Zhu Z, Liao X, Wu J, Cheng J, Zhang X, Mei H, Yang G. CRISPR-Cas13-mediated knockdown of lncRNA-GACAT3 inhibited cell proliferation and motility, and induced apoptosis by increasing p21, bax, and E-cadherin expression in bladder cancer. Front Mol Biosci. 2020;7:627774.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the General Program of National Natural Science Foundation of China (Grant No.81972278), the Youth Program of National Natural Science Foundation of China (Grant No.81802373), and 789 Outstanding Talent Program of SAHNMU (Grant 789ZYRC 202090147).

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KMW and JL conceptualized the manuscript. PPY and JD collected the literature, wrote the manuscript, and made the figures. JW and ZHM edited and made significant revisions to the manuscript. All authors read and approved the final manuscript.

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Correspondence to Keming Wang or Juan Li.

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Yang, P., Ding, J., Bian, Y. et al. Long non-coding RNAs and cancer mechanisms: Immune cells and inflammatory cytokines in the tumor microenvironment. Med Oncol 39, 108 (2022). https://doi.org/10.1007/s12032-022-01680-5

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  • DOI: https://doi.org/10.1007/s12032-022-01680-5

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