Obese Mouse Fat Cell-derived Extracellular Vesicles Transport miR-99a-5p to Mitigate the Proliferation and Migration of Non-small Cell Lung Cancer Cells


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Objective:Fat cells-derived extracellular vesicles (FC-EVs) play a role in regulating the tumor microenvironment in cancers by transporting RNAs. MicroRNAs (miRNAs) are vital regulators of cancer development. This study was conducted to explore the role of FC-EVs in the proliferation and migration of non-small cell lung cancer (NSCLC) cells, providing targets for NSCLC treatment.

Methods:The obese mouse model was established via high‐fat diet (HFD), followed by separation and characterization of FC-EVs (HFD-EVs). The levels of miR-99a-5p, precursor-miR-99a-5p, and heparan sulfate-glucosamine 3-sulfotransferase 3B1 (HS3ST3B1) were measured by RT-qPCR or Western blot assay. Cell proliferation and migration were evaluated by 3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide and wound healing assays. The expression of Cy3-labeled miR-99a-5p in A549 cells (one NSCLC cell line) was observed via confocal microscopy. The binding of miR-99a-5p to HS3ST3B1 was analyzed by the dual luciferase assay. Rescue experiments were performed to confirm the role of HS3ST3B1 in NSCLC cells.

Results:miR-99a-5p was upregulated in adipose tissues, FCs, and HFD-EVs. HFD-EVs mitigated the proliferation and migration of NSCLC cells. HFD-EVs transported miR-99a-5p into A549 cells, which upregulated miR-99a-5p expression and inhibited HS3ST3B1 expression in A549 cells. HS3ST3B1 overexpression reversed the inhibition of HFD-EVs on the proliferation and migration of NSCLC cells.

Conclusion:HFD-EVs transported miR-99a-5p into NSCLC cells and inhibited HS3ST3B1, thereby inhibiting proliferation and migration of NSCLC cells.

作者简介

Shengping Zhai

Department of General Practice, Yantai Yuhuangding Hospital Affiliated to Qingdao University

Email: info@benthamscience.net

Xiaoping Li

Department of Pulmonary and Critical Care Medicine, Yantai Yuhuangding Hospital Affiliated to Qingdao University

Email: info@benthamscience.net

Tiantian Lin

Respiratory Intensive Care Unit, Yantai Yuhuangding Hospital Affiliated to Qingdao University

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Barta, J.A.; Powell, C.A.; Wisnivesky, J.P. Global epidemiology of lung cancer. Ann. Glob. Health, 2019, 85(1), 1-16. doi: 10.5334/aogh.2419
  2. Duma, N.; Santana-Davila, R.; Molina, J.R. Non–small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin. Proc., 2019, 94(8), 1623-1640. doi: 10.1016/j.mayocp.2019.01.013 PMID: 31378236
  3. De Giglio, A.; Di Federico, A.; Nuvola, G.; Deiana, C.; Gelsomino, F. The landscape of immunotherapy in advanced NSCLC: Driving beyond PD-1/PD-L1 inhibitors (CTLA-4, LAG3, IDO, OX40, TIGIT, Vaccines). Curr. Oncol. Rep., 2021, 23(11), 126. doi: 10.1007/s11912-021-01124-9 PMID: 34453261
  4. Rossi, A.; Di Maio, M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: Optimal number of treatment cycles. Expert Rev. Anticancer Ther., 2016, 16(6), 653-660. doi: 10.1586/14737140.2016.1170596 PMID: 27010977
  5. Avgerinos, K.I.; Spyrou, N.; Mantzoros, C.S.; Dalamaga, M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism, 2019, 92, 121-135. doi: 10.1016/j.metabol.2018.11.001 PMID: 30445141
  6. Sommer, A.; Twig, G. The impact of childhood and adolescent obesity on cardiovascular risk in adulthood: A systematic review. Curr. Diab. Rep., 2018, 18(10), 91. doi: 10.1007/s11892-018-1062-9 PMID: 30167798
  7. Zhang, M.; Di Martino, J.S.; Bowman, R.L.; Campbell, N.R.; Baksh, S.C.; Simon-Vermot, T.; Kim, I.S.; Haldeman, P.; Mondal, C.; Yong-Gonzales, V.; Abu-Akeel, M.; Merghoub, T.; Jones, D.R.; Zhu, X.G.; Arora, A.; Ariyan, C.E.; Birsoy, K.; Wolchok, J.D.; Panageas, K.S.; Hollmann, T.; Bravo-Cordero, J.J.; White, R.M. Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov., 2018, 8(8), 1006-1025. doi: 10.1158/2159-8290.CD-17-1371 PMID: 29903879
  8. Vaitkus, J.A.; Celi, F.S. The role of adipose tissue in cancer-associated cachexia. Exp. Biol. Med., 2017, 242(5), 473-481. doi: 10.1177/1535370216683282 PMID: 27932592
  9. Quail, D.F.; Dannenberg, A.J. The obese adipose tissue microenvironment in cancer development and progression. Nat. Rev. Endocrinol., 2019, 15(3), 139-154. doi: 10.1038/s41574-018-0126-x PMID: 30459447
  10. Abels, E.R.; Breakefield, X.O. Introduction to extracellular vesicles: Biogenesis, RNA cargo selection, content, release, and uptake. Cell. Mol. Neurobiol., 2016, 36(3), 301-312. doi: 10.1007/s10571-016-0366-z PMID: 27053351
  11. La Camera, G.; Gelsomino, L.; Malivindi, R.; Barone, I.; Panza, S.; De Rose, D.; Giordano, F.; D’Esposito, V.; Formisano, P.; Bonofiglio, D.; Andò, S.; Giordano, C.; Catalano, S. Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity. Cancer Lett., 2021, 521, 155-168. doi: 10.1016/j.canlet.2021.08.021 PMID: 34425186
  12. Le Lay, S.; Rome, S.; Loyer, X.; Nieto, L. Adipocyte-derived extracellular vesicles in health and diseases: Nano-packages with vast biological properties. FASEB Bioadv., 2021, 3(6), 407-419. doi: 10.1096/fba.2020-00147 PMID: 34124596
  13. Yin, H.; Qiu, X.; Shan, Y.; You, B.; Xie, L.; Zhang, P.; Zhao, J.; You, Y. HIF‐1α downregulation of miR‐433‐3p in adipocyte derived exosomes contributes to NPC progression via targeting SCD1. Cancer Sci., 2021, 112(4), 1457-1470. doi: 10.1111/cas.14829 PMID: 33511729
  14. Parida, S.; Siddharth, S.; Sharma, D. Role of omentin in obesity paradox in lung cancer. Cancers , 2021, 13(2), 275. doi: 10.3390/cancers13020275 PMID: 33450975
  15. Zhang, X.; Liu, Y.; Shao, H.; Zheng, X. Obesity paradox in lung cancer prognosis: Evolving biological insights and clinical implications. J. Thorac. Oncol., 2017, 12(10), 1478-1488. doi: 10.1016/j.jtho.2017.07.022 PMID: 28757418
  16. Lee, S.S.; Cheah, Y.K. The interplay between microrNAs and cellular components of tumour microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) progression. J. Immunol. Res., 2019, 2019, 3046379. doi: 10.1155/2019/3046379 PMID: 30944831
  17. Vietsch, E.E.; Peran, I.; Suker, M.; van den Bosch, T.P.P. Sijde; Kros, J.M.; van Eijck, C.H.J.; Wellstein, A. Immune-related circulating miR-125b-5p and miR-99a-5p reveal a high recurrence risk group of pancreatic cancer patients after tumor resection. Appl. Sci. , 2019, 9(22), 4784. doi: 10.3390/app9224784 PMID: 34484811
  18. Liu, Y.; Li, B.; Yang, X.; Zhang, C. MiR‐99a‐5p inhibits bladder cancer cell proliferation by directly targeting mammalian target of rapamycin and predicts patient survival. J. Cell. Biochem., 2019, 120(12), 19330-19337. doi: 10.1002/jcb.27318 PMID: 30560585
  19. Sun, G.; Li, Z.; He, Z.; Wang, W.; Wang, S.; Zhang, X.; Cao, J.; Xu, P.; Wang, H.; Huang, X.; Xia, Y.; Lv, J.; Xuan, Z.; Jiang, T.; Fang, L.; Yang, J.; Zhang, D.; Xu, H.; Xu, Z. Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression. J. Exp. Clin. Cancer Res., 2020, 39(1), 246. doi: 10.1186/s13046-020-01758-w PMID: 33198772
  20. Wang, G.; Lu, Y.; Di, S.; Xie, M.; Jing, F.; Dai, X. miR 99a 5p inhibits glycolysis and induces cell apoptosis in cervical cancer by targeting RRAGD. Oncol. Lett., 2022, 24(1), 228. doi: 10.3892/ol.2022.13349 PMID: 35720506
  21. Siriwardhana, C.; Khadka, V.S.; Chen, J.J.; Deng, Y. Development of a miRNA-seq based prognostic signature in lung adenocarcinoma. BMC Cancer, 2019, 19(1), 34. doi: 10.1186/s12885-018-5206-8 PMID: 30621620
  22. Maemura, K.; Watanabe, K.; Ando, T.; Hiyama, N.; Sakatani, T.; Amano, Y.; Kage, H.; Nakajima, J.; Yatomi, Y.; Nagase, T.; Takai, D. Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma. Cancer Sci., 2018, 109(10), 3326-3335. doi: 10.1111/cas.13742 PMID: 30022565
  23. Yoshimura, A.; Sawada, K.; Nakamura, K.; Kinose, Y.; Nakatsuka, E.; Kobayashi, M.; Miyamoto, M.; Ishida, K.; Matsumoto, Y.; Kodama, M.; Hashimoto, K.; Mabuchi, S.; Kimura, T. Exosomal miR-99a-5p is elevated in sera of ovarian cancer patients and promotes cancer cell invasion by increasing fibronectin and vitronectin expression in neighboring peritoneal mesothelial cells. BMC Cancer, 2018, 18(1), 1065. doi: 10.1186/s12885-018-4974-5 PMID: 30396333
  24. Heianza, Y.; Krohn, K.; Xue, Q.; Meir, A.Y.; Ziesche, S.; Ceglarek, U.; Blüher, M.; Keller, M.; Kovacs, P.; Shai, I.; Qi, L. Changes in circulating microRNAs-99/100 and reductions of visceral and ectopic fat depots in response to lifestyle interventions: the CENTRAL trial. Am. J. Clin. Nutr., 2022, 116(1), 165-172. doi: 10.1093/ajcn/nqac070 PMID: 35348584
  25. Correia de Sousa, M.; Gjorgjieva, M.; Dolicka, D.; Sobolewski, C.; Foti, M. Deciphering miRNAs’ Action through miRNA Editing. Int. J. Mol. Sci., 2019, 20(24), 6249. doi: 10.3390/ijms20246249 PMID: 31835747
  26. Shi, M.; Zhang, Z.; Jiang, H.; Wang, Y. Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a novel regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer. J. Cancer Res. Ther., 2018, 14(1), 24-29. doi: 10.4103/jcrt.JCRT_659_17 PMID: 29516954
  27. Jones-Bolin, S. Guidelines for the care and use of laboratory animals in biomedical research. Curr. Protoc. Pharmacol. Appendix, 2012, 4, 4B.
  28. Zhu, R.; Wei, J.; Liu, H.; Liu, C.; Wang, L.; Chen, B.; Li, L.; Jia, Q.; Tian, Y.; Li, R.; Zhao, D.; Mo, F.; Li, Y.; Gao, S.; Wang, X.D.; Zhang, D. Lycopene attenuates body weight gain through induction of browning via regulation of peroxisome proliferator-activated receptor γ in high-fat diet-induced obese mice. J. Nutr. Biochem., 2020, 78, 108335. doi: 10.1016/j.jnutbio.2019.108335 PMID: 31978713
  29. Fu, Q.; Li, Y.; Jiang, H.; Shen, Z.; Gao, R.; He, Y.; Liu, Y.; Xu, K.; Yang, T. Hepatocytes derived extracellular vesicles from high-fat diet induced obese mice modulate genes expression and proliferation of islet β cells. Biochem. Biophys. Res. Commun., 2019, 516(4), 1159-1166. doi: 10.1016/j.bbrc.2019.06.124 PMID: 31284955
  30. Gao, J.; Li, X.; Wang, Y.; Cao, Y.; Yao, D.; Sun, L.; Qin, L.; Qiu, H.; Zhan, X. Adipocyte-derived extracellular vesicles modulate appetite and weight through mTOR signalling in the hypothalamus. Acta Physiol., 2020, 228(2), e13339. doi: 10.1111/apha.13339 PMID: 31278836
  31. Liu, S.; Chu, L.; Xie, M.; Ma, L.; An, H.; Zhang, W.; Deng, J. miR-92a-3p promoted EMT via targeting LATS1 in cervical cancer stem cells. Front. Cell Dev. Biol., 2021, 9, 757747. doi: 10.3389/fcell.2021.757747 PMID: 34869346
  32. Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(D1), D92-D97. doi: 10.1093/nar/gkt1248 PMID: 24297251
  33. Agarwal, V.; Bell, G.W.; Nam, J.W.; Bartel, D.P. Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015, 4, e05005. doi: 10.7554/eLife.05005 PMID: 26267216
  34. Chen, Y.; Wang, X. miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res., 2020, 48(D1), D127-D131. doi: 10.1093/nar/gkz757 PMID: 31504780
  35. Sticht, C.; De La Torre, C.; Parveen, A.; Gretz, N. miRWalk: An online resource for prediction of microRNA binding sites. PLoS One, 2018, 13(10), e0206239. doi: 10.1371/journal.pone.0206239 PMID: 30335862
  36. Mitra, A.; Yoshida-Court, K.; Solley, T.N.; Mikkelson, M.; Yeung, C.L.A.; Nick, A.; Lu, K.; Klopp, A.H. Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells. Sci. Rep., 2021, 11(1), 9149. doi: 10.1038/s41598-021-88163-1 PMID: 33911091
  37. Urabe, F.; Kosaka, N.; Ito, K.; Kimura, T.; Egawa, S.; Ochiya, T. Extracellular vesicles as biomarkers and therapeutic targets for cancer. Am. J. Physiol. Cell Physiol., 2020, 318(1), C29-C39. doi: 10.1152/ajpcell.00280.2019 PMID: 31693397
  38. Zhou, G.; Gu, Y.; Zhou, F.; Zhang, H.; Zhang, M.; Zhang, G.; Wu, L.; Hua, K.; Ding, J. Adipocytes-derived extracellular vesicle-miR-26b promotes apoptosis of cumulus cells and induces polycystic ovary syndrome. Front. Endocrinol., 2022, 12, 789939. doi: 10.3389/fendo.2021.789939 PMID: 35222263
  39. Clement, E.; Lazar, I.; Attané, C.; Carrié, L.; Dauvillier, S.; Ducoux-Petit, M.; Esteve, D.; Menneteau, T.; Moutahir, M.; Le Gonidec, S.; Dalle, S.; Valet, P.; Burlet-Schiltz, O.; Muller, C.; Nieto, L. Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J., 2020, 39(3), e102525. doi: 10.15252/embj.2019102525 PMID: 31919869
  40. Moraes, J.A.; Encarnação, C.; Franco, V.A.; Xavier Botelho, L.G.; Rodrigues, G.P.; Ramos-Andrade, I.; Barja-Fidalgo, C.; Renovato-Martins, M. Adipose tissue-derived extracellular vesicles and the tumor microenvironment: revisiting the hallmarks of cancer. Cancers , 2021, 13(13), 3328. doi: 10.3390/cancers13133328 PMID: 34283044
  41. Au Yeung, C.L.; Co, N.N.; Tsuruga, T.; Yeung, T.L.; Kwan, S.Y.; Leung, C.S.; Li, Y.; Lu, E.S.; Kwan, K.; Wong, K.K.; Schmandt, R.; Lu, K.H.; Mok, S.C. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat. Commun., 2016, 7(1), 11150. doi: 10.1038/ncomms11150 PMID: 27021436
  42. Liu, Y.; Tan, J.; Ou, S.; Chen, J.; Chen, L. Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis. J. Physiol. Biochem., 2019, 75(3), 391-401. doi: 10.1007/s13105-019-00692-6 PMID: 31321740
  43. Fan, X.; Wang, J.; Qin, T.; Zhang, Y.; Liu, W.; Jiang, K.; Huang, D. Exosome miR‐27a‐3p secreted from adipocytes targets ICOS to promote antitumor immunity in lung adenocarcinoma. Thorac. Cancer, 2020, 11(6), 1453-1464. doi: 10.1111/1759-7714.13411 PMID: 32212417
  44. Guo, T.; Wang, Y.; Jia, J.; Mao, X.; Stankiewicz, E.; Scandura, G.; Burke, E.; Xu, L.; Marzec, J.; Davies, C.R.; Lu, J.J.; Rajan, P.; Grey, A.; Tipples, K.; Hines, J.; Kudahetti, S.; Oliver, T.; Powles, T.; Alifrangis, C.; Kohli, M.; Shaw, G.; Wang, W.; Feng, N.; Shamash, J.; Berney, D.; Wang, L.; Lu, Y.J. The identification of plasma exosomal miR-423-3p as a potential predictive biomarker for prostate cancer castration-resistance development by plasma exosomal miRNA sequencing. Front. Cell Dev. Biol., 2021, 8, 602493. doi: 10.3389/fcell.2020.602493 PMID: 33490068
  45. Yu, S.; Zhang, C.; Dong, F.; Zhang, Y. miR-99a suppresses the metastasis of human non-small cell lung cancer cells by targeting AKT1 signaling pathway. J. Cell. Biochem., 2015, 116(2), 268-276. doi: 10.1002/jcb.24965 PMID: 25187230
  46. Li, Y.; Shi, B.; Dong, F.; Zhu, X.; Liu, B.; Liu, Y. Long non-coding RNA DLEU1 promotes cell proliferation, invasion, and confers cisplatin resistance in bladder cancer by regulating the miR-99b/HS3ST3B1 axis. Front. Genet., 2019, 10, 280. doi: 10.3389/fgene.2019.00280 PMID: 30984249
  47. Li, Y.; Shi, B.; Dong, F.; Zhu, X.; Liu, B.; Liu, Y. LncRNA KCNQ1OT1 facilitates the progression of bladder cancer by targeting MiR-218-5p/HS3ST3B1. Cancer Gene Ther., 2021, 28(3-4), 212-220. doi: 10.1038/s41417-020-00211-6 PMID: 32820233
  48. Zhang, L.; Song, K.; Zhou, L.; Xie, Z.; Zhou, P.; Zhao, Y.; Han, Y.; Xu, X.; Li, P. Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1 (HS3ST3B1) promotes angiogenesis and proliferation by induction of VEGF in acute myeloid leukemia cells. J. Cell. Biochem., 2015, 116(6), 1101-1112. doi: 10.1002/jcb.25066 PMID: 25536282

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