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研究生：	許修瑞 Hsu, Xiu-Rui
論文名稱：	胞外泌體中的長鏈非編碼RNA MLETA1透過調節非小細胞肺癌中的miR-186-5p/EGFR和miR-497-5p/IGF1R路徑促進腫瘤進展和轉移 Exosomal long noncoding RNA MLETA1 promotes tumor progression and metastasis by regulating the miR‑186‑5p/EGFR and miR‑497‑5p/IGF1R axes in non‑small cell lung cancer
指導教授：	洪澤民 Hong, Tse-Ming
學位類別：	博士 Doctor
系所名稱：	醫學院 - 臨床醫學研究所 Institute of Clinical Medicine
論文出版年：	2024
畢業學年度：	112
語文別：	英文
論文頁數：	116
中文關鍵詞：	lnc-MLETA1 、肺癌轉移、胞外泌體、miR-186-5p 、miR-497-5p 、上皮成長因子接受器、胰島素樣生長因子1受體
外文關鍵詞：	lnc-MLETA1, Lung cancer metastasis, exosome, miR-186-5p, miR-497-5p, IGF1R, EGFR
相關次數：	點閱：53 下載：0
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肺癌是全世界最常見且死亡率最高的癌症，腫瘤轉移約佔肺癌相關死亡的 90%。腫瘤來源的胞外泌體透過傳遞對該過程至關重要的分子而成為轉移的潛在促進劑。然而，胞外泌體長鏈非編碼RNA（lncRNA）在肺癌轉移中的作用和機制有很大程度地不清楚。我們的研究發現，來自高轉移性肺癌細胞的胞外泌體增強了低轉移性肺癌細胞的遷移和侵襲能力。透過胞外泌體lncRNA定序（lncRNA-seq），我們發現了一種新型lncRNA，lnc-MLETA1，它在高度轉移細胞及其胞外泌體中大量表現。lnc-MLETA1的過度表現增強了肺癌細胞的遷移和侵襲，而lnc-MLETA1的抑制則降低了細胞的運動和轉移。有趣的是，胞外泌體所介導的lnc-MLETA1傳遞促進了肺癌細胞的運動和轉移，而用lnc-MLETA1專一性的LNA可以消除這種現象。在機制方面，lnc-MLETA1透過與miR-186-5p 和 miR-497-5p 的交互作用來調節EGFR和IGF1R的表達，從而促進細胞運動。臨床數據表明，肺癌患者血漿中胞外泌體的lnc-MLETA1表現與轉移呈正相關，表明其具有作為肺癌診斷和治療的預後生物標記和治療標靶的潛力。

Lung cancer stands as the most prevalent and deadliest form of cancer worldwide, with tumor metastasis accounting for about 90% of lung cancer-related deaths. Tumor-derived exosomes have emerged as potential facilitators of metastasis by delivering molecules crucial for this process. However, the role and mechanism underlying exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely elusive. Our study reveals that exosomes from highly metastatic lung cancer cells enhance the migration and invasion capabilities of low-metastatic lung cancer cells. Through exosomal lncRNA sequencing (lncRNA-seq), we identified a novel lncRNA, lnc-MLETA1, upregulated in highly metastatic cells and their exosomes. Overexpression of lnc-MLETA1 amplified lung cancer cell migration and invasion, while its knockdown decreased cell motility and metastasis. Interestingly, exosome-mediated transfer of lnc-MLETA1 promoted lung cancer cell motility and metastasis, which was abrogated by targeting lnc-MLETA1 with an LNA. Mechanistically, lnc-MLETA1 modulated EGFR and IGF1R expression by binding miR-186-5p and miR-497-5p, thereby facilitating cell motility. Clinical data indicated a positive correlation between plasma exosomal lnc-MLETA1 levels and metastasis in lung cancer patients, suggesting its potential as a prognostic biomarker and therapeutic target for lung cancer diagnosis and treatment.

中文摘要	I
Abstract	II
Acknowledgement	III
Contents	IV
Abbreviations	IX
Introduction	1
Lung cancer	1
Tumor metastasis	1
Exosomes	2
Exosomes in metastasis	3
Long noncoding RNAs (lncRNAs)	3
LncRNAs in metastasis	4
Rationale and specific aims	6
Material and methods	7
Cell culture	7
Conditioned Media Harvest	7
Purification of exosomes by differential ultracentrifugation	7
Transmission electron microscopy	7
Nanoparticle tracking analysis	8
Western blot analysis	8
In vitro wound-healing assay	9
Transwell invasion assay	9
RNA-sequencing analysis	9
Cell proliferation assay	10
Soft-agar colony formation assay	10
Cellular RNA isolation	10
Exosomal RNA isolation	11
Quantitative real-time polymerase chain reaction (qRT-PCR)	11
Plasmid construction	11
Transfection	11
MS2-tagged RNA afﬁnity puriﬁcation	12
Xenograft animal model	12
Statistical analysis	13
Ethics approval and consent to participate	13
Results	14
Exosomes secreted from highly metastatic lung cancer cells enhance the movement and invasive abilities of lung cancer cells with low metastatic potential.	14
lnc-MLETA1 facilitates the migratory and invasive capabilities of lung cancer cells in vitro.	15
Exosome-transmitted lnc-MLETA1 augment the migratory and invasive capabilities of lung cancer cells in vitro.	17
Exosome-shuttling lnc-MLETA1 stimulates lung cancer metastasis in vivo.	18
lnc-MLETA1 affects lung cancer cell migration via binding miR-186-5p and miR-497-5p.	19
lnc-MLETA1 regulates lung cancer cell migration by influencing the miR-186-5p/EGFR and miR-497-5p/IGF1R pathway.	20
Exosomal lnc-MLETA1 positively correlates with lung cancer metastasis.	23
Discussion	25
Conclusions	29
References	30
Figures	38
Figure 1. The increased migratory and invasive abilities of CL1-0 cells are primarily due to the transmission of exosomes from CL1-5 cells within the extracellular microenvironment.	39
Figure 2. Characterization of exosomes isolated from the conditioned media of CL1-0 and CL1-5 cells by ultracentrifugation.	40
Figure 3. Exosomes derived from CL1-0 and CL1-5 cells can be taken up by CL1-0 cells.	41
Figure 4. Exosomes derived from high metastatic lung cancer cells promotes cell migration and invasion of low metastatic lung cancer cells.	42
Figure 5. lnc-MLETA1 is upregulated in CL1-5 exosomes.	43
Figure 6. lnc-MLETA1 is upregulated in CL1-5 cells and exosomes.	44
Figure 7. lnc-MLETA1 is upregulated in highly metastatic lung cancer cells.	45
Figure 8. Characterization of lnc-MLETA1.	46
Figure 9. There is a more open and accessible chromatin structure in the genomic region of lnc-MLETA1.	47
Figure 10. lnc-MLETA1 is not significantly correlated with patients’ survival in AML, breast cancer, colon cancer, gastric cancer, myeloma, and ovarian cancer.	48
Figure 11. Overexpression of lnc-MLETA1 augments cell migration and invasion of lung cancer in vitro.	49
Figure 12. Knockdown of lnc-MLETA1 attenuates cell migration and invasion of lung cancer in vitro.	51
Figure 13. Knockdown of lnc-MLETA1 inhibits cell motility of lung cancer in vitro.	53
Figure 14. Knockdown of lnc-MLETA1 suppresses cell growth of lung cancer.	54
Figure 15. Knockdown of lnc-MLETA1 suppresses anchorage-independent growth ability of lung cancer cell.	55
Figure 16. The transmission of lnc-MLETA1 is mediated by exosomes.	56
Figure 17. Exosome-transmitted lnc-MLETA1 is uptake by CL1-0 cells.	57
Figure 18. Exosomal lnc-MLETA1 promotes lung cancer cell migration and invasion in vitro.	58
Figure 19. Targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility in vitro.	59
Figure 20. lnc-MLETA1 promotes lung cancer metastasis in vivo.	61
Figure 21. Exosomal lnc-MLETA1 facilitates lung cancer metastasis in vivo.	63
Figure 22. Exosomal lnc-MLETA1 augments tumor growth in vivo.	65
Figure 23. lnc-MLETA1 is predominantly located in the cytoplasm.	67
Figure 24. lnc-MLETA1 may interact with miRNA.	68
Figure 25. lnc-MLETA1 contains binding sequences for several miRNAs, including miR-186-5p, miR-497-5p, miR-127-5p and miR-375.	69
Figure 26. lnc-MLETA1 can interact with miR-186-5p and miR-497-5p but not miR-127-5p and miR-375.	70
Figure 27. Overexpression of lnc-MLETA1 significantly increased the number of migrated CL1-0 cells, but this effect was abolished by overexpression of miR-186-5p and miR-497-5p.	72
Figure 28. miR-186-5p and miR-497-5p mimics significantly decreased the migrated cell number in CL1-5 cells, but this effect could be rescued by overexpression of lnc-MLETA1.	74
Figure 29. Regulatory relationships between lnc-MLETA1 and miR-186-5p or miR-497-5p.	75
Figure 30. Top 50 most increased and decreased genes among 778 differentially-expressed genes.	76
Figure 31. Gene ontology (GO) analysis indicates 20-term enrichment, such as focal adhesion, integrin complex, and apical plasma membrane.	77
Figure 32. GSEA indicates that lnc-MLETA1 is involved in the metastatic process and regulates the expression of metastasis-related genes and target genes of miR-186-5p and miR-497-5p.	78
Figure 33. The intersection of predicted target genes of miR-186-5p and miR-497-5p and downregulated genes following lnc-MLETA1 silencing.	79
Figure 34. lnc-MLETA1 regulate the mRNA and protein expression of EGFR and IGF1R.	80
Figure 35. GSEA indicates that lnc-MLETA1 regulates the EGFR and IGF1R signaling pathways.	81
Figure 36. EGFR and IGF1R can be downregulated by miR-186-5p and miR-497-5p, respectively.	82
Figure 37. The prediction of binding sites of miR-186-5p on the EGFR 3’UTR and miR-497-5p on the IGF1R 3’UTR.	83
Figure 38. EGFR and IGF1R are the direct downstream targets of miR-186-5p and miR-497-5p, respectively.	84
Figure 39. lncRNA‒miRNA interactions can regulate the expression of EGFR and IGF1R.	85
Figure 40. Knockdown of EGFR and IGF1R attenuates lung cancer cell migration.	86
Figure 41. lnc-MLETA1 facilitates cell motility via EGFR and IGF1R.	88
Figure 42. The delivery of exosomes from high-metastatic cancer cells affects low-metastatic cancer migration by upregulating EGFR and IGF1R.	89
Figure 43. The expression of lnc-MLETA1, EGFR, and IGF1R is upregulated in lung cancer tissues.	90
Figure 44. lnc-MLETA1 expression is positively correlated with EGFR and IGF1R expression in lung cancer tissues.	91
Figure 45. Lung cancer patients with both elevated lnc-MLETA1 and EGFR or IGF1R had significantly poorer survival.	92
Figure 46. The expression of miR-186-5p and miR-497-5p is downregulated in lung cancer tissues.	93
Figure 47. miR-186-5p and miR-497-5p expression is negatively correlated with expression of the target genes EGFR and IGF1R in lung cancer tissues.	94
Figure 48. Lung cancer patients with high expression of miR-186-5p and miR-497-5p had significantly better survival.	95
Figure 49. Receiver operating characteristic (ROC) analysis indicates that plasma exosomal lnc-MLETA1 could be a diagnostic biomarker for lung cancer metastasis and discriminated lung cancer patients from healthy subjects.	96
Figure 50. The levels of lnc-MLETA1 in metastatic tissues were upregulated in lung cancer patients.	97
Figure 51. Schematic diagram of lnc-MLETA1-based regulatory mechanism in lung cancer metastasis.	98
Tables	99
Table 1 Correlations between exosomal lnc-MLETA1 expression and clinicopathological features.	99
Table 2 Correlations between exosomal lnc-MLETA1 expression and lung cancer diagnosis.	100
Table 3 Sequences of primers/shRNA/LNA used in this study.	101
Table 4 Primary antibodies used for immunoblotting in this study.	103
                                    

1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49.
2. Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics. Adv Exp Med Biol. 2016;893:1-19.
3. Ali A, Goffin JR, Arnold A, Ellis PM. Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol. 2013;20(4):e300-6.
4. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31-46.
5. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging Biological Principles of Metastasis. Cell. 2017;168(4):670-91.
6. Ganesh K, Massagué J. Targeting metastatic cancer. Nat Med. 2021;27(1):34-44.
7. Altorki NK, Markowitz GJ, Gao D, Port JL, Saxena A, Stiles B, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19(1):9-31.
8. Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y, et al. Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. 2019;21(4):498-510.
9. Rodrigues G, Hoshino A, Kenific CM, Matei IR, Steiner L, Freitas D, et al. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat Cell Biol. 2019;21(11):1403-12.
10. Qi M, Xia Y, Wu Y, Zhang Z, Wang X, Lu L, et al. Lin28B-high breast cancer cells promote immune suppression in the lung pre-metastatic niche via exosomes and support cancer progression. Nat Commun. 2022;13(1):897.
11. Chen C, Luo Y, He W, Zhao Y, Kong Y, Liu H, et al. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. J Clin Invest. 2020;130(1):404-21.
12. Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97(2):329-39.
13. Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33(3):967-78.
14. Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255-89.
15. Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;Chapter 3:Unit 3.22.
16. Isola AL, Chen S. Exosomes: The Messengers of Health and Disease. Curr Neuropharmacol. 2017;15(1):157-65.
17. Robbins PD, Morelli AE. Regulation of Immune Responses by Extracellular Vesicles. Nat Rev Immunol. 2014;14(3):195-208.
18. Imjeti NS, Menck K, Egea-Jimenez AL, Lecointre C, Lembo F, Bouguenina H, et al. Syntenin mediates SRC function in exosomal cell-to-cell communication. Proc Natl Acad Sci U S A. 2017.
19. Xu B, Zhang Y, Du XF, Li J, Zi HX, Bu JW, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 2017;27(7):882-97.
20. Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542(7642):450-5.
21. Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 2013;32(3-4):623-42.
22. Ichim TE, Zhong Z, Kaushal S, Zheng X, Ren X, Hao X, et al. Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J Transl Med. 2008;6:37.
23. Xiao T, Zhang W, Jiao B, Pan CZ, Liu X, Shen L. The role of exosomes in the pathogenesis of Alzheimer' disease. Transl Neurodegener. 2017;6:3.
24. Yang VK. Circulating exosome microRNA associated with heart failure secondary to myxomatous mitral valve disease in a naturally occurring canine model. 2017;6(1).
25. Sato K, Meng F, Glaser S, Alpini G. Exosomes in liver pathology. J Hepatol. 2016;65(1):213-21.
26. Au Yeung CL, Co NN, Tsuruga T, Yeung TL, Kwan SY, Leung CS, et al. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun. 2016;7:11150.
27. Whiteside TL. Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans. 2013;41(1):245-51.
28. Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560(7718):382-6.
29. Syn N, Wang L, Sethi G, Thiery JP, Goh BC. Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance. Trends Pharmacol Sci. 2016;37(7):606-17.
30. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329-35.
31. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012;109(31):E2110-6.
32. Ye SB, Li ZL, Luo DH, Huang BJ, Chen YS, Zhang XS, et al. Tumor-derived exosomes promote tumor progression and T-cell dysfunction through the regulation of enriched exosomal microRNAs in human nasopharyngeal carcinoma. Oncotarget. 2014;5(14):5439-52.
33. Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol. 2011;187(2):676-83.
34. Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest. 2016;126(4):1216-23.
35. Schmitt AM, Chang HY. Long Noncoding RNAs in Cancer Pathways. Cancer Cell. 2016;29(4):452-63.
36. 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.
37. Xue ST, Zheng B, Cao SQ, Ding JC, Hu GS, Liu W, et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Mol Cancer. 2022;21(1):69.
38. Wang X, Cheng H, Zhao J, Li J, Chen Y, Cui K, et al. Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer. Mol Cancer. 2022;21(1):210.
39. Zhou Y, Shao Y, Hu W, Zhang J, Shi Y, Kong X, et al. A novel long noncoding RNA SP100-AS1 induces radioresistance of colorectal cancer via sponging miR-622 and stabilizing ATG3. Cell Death Differ. 2023;30(1):111-24.
40. Zhou M, Pan S, Qin T, Zhao C, Yin T, Gao Y, et al. LncRNA FAM83H-AS1 promotes the malignant progression of pancreatic ductal adenocarcinoma by stabilizing FAM83H mRNA to protect β-catenin from degradation. J Exp Clin Cancer Res. 2022;41(1):288.
41. Zhu Q, Zhang C, Qu T, Lu X, He X, Li W, et al. MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc-Mediated Cell-Cycle Progression and Proliferation in Lung Cancer. Cancer Res. 2022;82(23):4340-58.
42. Fang Y, Fullwood MJ. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics. 2016;14(1):42-54.
43. Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. J Cell Biol. 2021;220(2).
44. Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA. Long noncoding RNAs in cancer metastasis. Nat Rev Cancer. 2021;21(7):446-60.
45. Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25(5):666-81.
46. Qu L, Wu Z, Li Y, Xu Z, Liu B, Liu F, et al. A feed-forward loop between lncARSR and YAP activity promotes expansion of renal tumour-initiating cells. Nat Commun. 2016;7:12692.
47. Li D, She J, Hu X, Zhang M, Sun R, Qin S. The ELF3-regulated lncRNA UBE2CP3 is over-stabilized by RNA-RNA interactions and drives gastric cancer metastasis via miR-138-5p/ITGA2 axis. Oncogene. 2021;40(35):5403-15.
48. Wu N, Jiang M, Liu H, Chu Y, Wang D, Cao J, et al. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-β/SMAD2/3 signaling pathway. Cell Death Differ. 2021;28(1):219-32.
49. Wen S, Wei Y, Zen C, Xiong W, Niu Y, Zhao Y. Long non-coding RNA NEAT1 promotes bone metastasis of prostate cancer through N6-methyladenosine. Mol Cancer. 2020;19(1):171.
50. Jiang C, Zhang N, Hu X, Wang H. Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms. Mol Cancer. 2021;20(1):117.
51. Wang PS, Chou CH, Lin CH, Yao YC, Cheng HC, Li HY, et al. A novel long non-coding RNA linc-ZNF469-3 promotes lung metastasis through miR-574-5p-ZEB1 axis in triple negative breast cancer. Oncogene. 2018;37(34):4662-78.
52. Yang B, Feng X, Liu H, Tong R, Wu J, Li C, et al. High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma. Oncogene. 2020;39(42):6529-43.
53. Wu K, Feng J, Lyu F, Xing F, Sharma S, Liu Y, et al. Exosomal miR-19a and IBSP cooperate to induce osteolytic bone metastasis of estrogen receptor-positive breast cancer. Nat Commun. 2021;12(1):5196.
54. Qu L, Ding J, Chen C, Wu ZJ, Liu B, Gao Y, et al. Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Cancer Cell. 2016;29(5):653-68.
55. Zhu J, Cai T, Zhou J, Du W, Zeng Y, Liu T, et al. CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer. J Exp Clin Cancer Res. 2021;40(1):192.
56. Sun Y, Gao Y, Dong M, Li J, Li X, He N, et al. Kremen2 drives the progression of non-small cell lung cancer by preventing SOCS3-mediated degradation of EGFR. J Exp Clin Cancer Res. 2023;42(1):140.
57. Alfaro-Arnedo E, López IP, Piñeiro-Hermida S, Canalejo M, Gotera C, Sola JJ, et al. IGF1R acts as a cancer-promoting factor in the tumor microenvironment facilitating lung metastasis implantation and progression. Oncogene. 2022;41(28):3625-39.
58. Hua J, Wang X, Ma L, Li J, Cao G, Zhang S, et al. CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis. Mol Cancer. 2022;21(1):123.
59. Yin L, Liu X, Shao X, Feng T, Xu J, Wang Q, et al. The role of exosomes in lung cancer metastasis and clinical applications: an updated review. J Transl Med. 2021;19(1):312.
60. Huang WJ, Guo SB, Shi H, Li XL, Zhu Y, Li M, et al. The β-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 axis promotes adult T-cell lymphoblastic lymphoma progression and chemoresistance. J Exp Clin Cancer Res. 2023;42(1):105.
61. Zhang N, Wang B, Ma C, Zeng J, Wang T, Han L, et al. LINC00240 in the 6p22.1 risk locus promotes gastric cancer progression through USP10-mediated DDX21 stabilization. J Exp Clin Cancer Res. 2023;42(1):89.
62. Huang W, Li H, Yu Q, Xiao W, Wang DO. LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond. J Exp Clin Cancer Res. 2022;41(1):100.
63. Donker RB, Mouillet JF, Nelson DM, Sadovsky Y. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol Hum Reprod. 2007;13(4):273-9.
64. Wu S, Luo M, To KKW, Zhang J, Su C, Zhang H, et al. Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer. Mol Cancer. 2021;20(1):17.
65. Yang H, Wen L, Zhao C, Li X, Shan C, Liu D, et al. EGFR amplification is a putative resistance mechanism for NSCLC-LM patients with TKI therapy and is associated with poor outcome. Front Oncol. 2022;12:902664.
66. Al-Saad S, Richardsen E, Kilvaer TK, Donnem T, Andersen S, Khanehkenari M, et al. The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of patients with non-small-cell lung cancer. PLoS One. 2017;12(7):e0181527.
67. Wang J, Zhang Y, Ge F. MiR-186 Suppressed Growth, Migration, and Invasion of Lung Adenocarcinoma Cells via Targeting Dicer1. J Oncol. 2021;2021:6217469.
68. Huang X, Wang L, Liu W, Li F. MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2. Oncol Lett. 2019;17(3):3425-31.
69. Herkt M, Thum T. Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics. Mol Ther. 2021;29(2):521-39.
70. Shadid M, Badawi M, Abulrob A. Antisense oligonucleotides: absorption, distribution, metabolism, and excretion. Expert Opin Drug Metab Toxicol. 2021;17(11):1281-92.
71. Bennett CF, Kordasiewicz HB, Cleveland DW. Antisense Drugs Make Sense for Neurological Diseases. Annu Rev Pharmacol Toxicol. 2021;61:831-52.
72. Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020;19(10):673-94.
73. Alhamadani F, Zhang K, Parikh R, Wu H, Rasmussen TP, Bahal R, et al. Adverse Drug Reactions and Toxicity of the Food and Drug Administration-Approved Antisense Oligonucleotide Drugs. Drug Metab Dispos. 2022;50(6):879-87.
74. Zhou T, Kim Y, MacLeod AR. Targeting Long Noncoding RNA with Antisense Oligonucleotide Technology as Cancer Therapeutics. Methods Mol Biol. 2016;1402:199-213.
75. Tan DSW, Chong FT, Leong HS, Toh SY, Lau DP, Kwang XL, et al. Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma. Nat Med. 2017;23(10):1167-75.

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