CLC number:
On-line Access: 2022-11-15
Received: 2022-03-08
Revision Accepted: 2022-07-22
Crosschecked: 2022-11-16
Cited: 0
Clicked: 1008
Citations: Bibtex RefMan EndNote GB/T7714
https://orcid.org/0000-0003-2943-9220
Shipeng CHEN, Lian GUAN, Xu ZHAO, Jing YANG, Longqing CHEN, Mengmeng GUO, Juanjuan ZHAO, Chao CHEN, Ya ZHOU, Yong HAN, Lin XU. Optimized thyroid transcription factor-1 core promoter-driven microRNA-7 expression effectively inhibits the growth of human non-small-cell lung cancer cells[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200116 @article{title="Optimized thyroid transcription factor-1 core promoter-driven microRNA-7 expression effectively inhibits the growth of human non-small-cell lung cancer cells", %0 Journal Article TY - JOUR
优化的TTF-1核心启动子驱动miRNA-7表达有效抑制人非小细胞肺癌细胞的生长1贵州省基因检测与治疗特色重点实验室暨贵州省生物治疗人才基地,中国遵义市,563000 2遵义医科大学免疫学教研室,中国遵义市,563000 3遵义医科大学医学物理系,中国遵义市,563000 4遵义医科大学生理学教研室,中国遵义市,563000 概要:靶向基因治疗是一种很有前景的肺癌治疗方法。在前期工作中,我们报道了由甲状腺转录因子-1(TTF-1)启动子调控微小RNA-7(miR-7)的靶向表达可在体外和体内抑制人肺癌细胞的生长,但干预效率有待进一步提高。在本研究中,我们通过5’缺失分析鉴定了TTF-1的核心启动子(从−1299 bp到−871 bp),并筛选出潜在的结合转录因子核因子-1(NF-1)和激活蛋白-1(AP-1)。进一步分析的结果表明:NF-1的表达水平,而非AP-1的表达水平,与人非小细胞肺癌(NSCLC)细胞中TTF-1核心启动子的活性呈正相关。此外,NF-1的沉默可以降低由TTF-1核心启动子调控的miR-7的表达。重要的是,我们在TTF-1核心启动子的序列上优化了四个不同的序列(称为optTTF-1启动子)以形成额外的NF-1结合位点(TGGCA),并通过电泳迁移率实验(EMSA)分析验证了NF-1对optTTF-1启动子的结合效率。通进一步研究,结果显示optTTF-1启动子可更有效地驱动miR-7表达并在体外抑制人NSCLC细胞的生长,同时减少Ⅰ型辅酶脱氢酶1α亚复合物4(NDUFA4)/蛋白激酶B(Akt)通路转导。optTTF-1启动子驱动的miR-7表达同样也可有效地抑制人NSCLC异种移植模型中肿瘤细胞的体内生长和转移。最后,模型动物的心脏、肝脏和脾脏等重要组织和器官的生物学指标和组织学未见明显变化。总之,本研究揭示了优化的TTF-1启动子可更有效地调控miR-7表达来抑制人NSCLC细胞的生长,为开发基于miRNA的靶向基因治疗临床肺癌提供了新的实验基础。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
Reference[1]AmreddyN, BabuA, MuralidharanR, et al., 2017. Polymeric nanoparticle-mediated gene delivery for lung cancer treatment. Top Curr Chem (Cham), 375(2):35. [2]BillietC, PeetersS, DecaluwéH, et al., 2016. Postoperative radiotherapy for lung cancer: is it worth the controversy? Cancer Treat Rev, 51:10-18. [3]BucherK, Rodríguez-BocanegraE, DauletbekovD, et al., 2021. Immune responses to retinal gene therapy using adeno-associated viral vectors-implications for treatment success and safety. Prog Retin Eye Res, 83:100915. [4]CaoQ, MaoZD, ShiYJ, et al., 2016. MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway. Oncotarget, 7(47):77468-77481. [5]ChanBA, CowardJIG, 2013. Chemotherapy advances in small-cell lung cancer. J Thorac Dis, 5(S5):S565-S578. [6]ChandlerRJ, VenturoniLE, LiaoJ, et al., 2021. Promoterless, nuclease-free genome editing confers a growth advantage for corrected hepatocytes in mice with methylmalonic acidemia. Hepatology, 73(6):2223-2237. [7]ChenHZ, GuoMM, YueDX, et al., 2021. MicroRNA-7 negatively regulates Toll-like receptor 4 signaling pathway through FAM177A. Immunology, 162(1):44-57. [8]ChenSP, WangY, LiDM, et al., 2022. Mechanisms controlling microRNA expression in tumor. Cells, 11(18):2852. [9]DaninoYM, EvenD, IdesesD, et al., 2015. The core promoter: at the heart of gene expression. Biochim Biophys Acta, 1849(8):1116-1131. [10]DuX, XiaoJJ, FuXF, et al., 2021. A proteomic analysis of Bcl-2 regulation of cell cycle arrest: insight into the mechanisms. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(10):839-855. [11]DuX, ZhangJQ, LiuL, et al., 2022. A novel anticancer prop [12]erty of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(4):286-299. [13]DziadziuszkoR, KrebsMG, de BraudF, et al., 2021. Updated integrated analysis of the efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small-cell lung cancer. J Clin Oncol, 39(11):1253-1263. [14]EvenDY, KedmiA, IdesesD, et al., 2017. Functional screening of core promoter activity. In: Gould D (Ed.), Mammalian Synthetic Promoters. Humana, New York, p.77-91. [15]FukazawaT, MaedaY, DurbinML, et al., 2007. Pulmonary adenocarcinoma-targeted gene therapy by a cancer- and tissue-specific promoter system. Mol Cancer Ther, 6(1):244-252. [16]FulzeleSV, ChatterjeeA, ShaikMS, et al., 2006. Inhalation delivery and anti-tumor activity of celecoxib in human orthotopic non-small cell lung cancer xenograft model. Pharm Res, 23(9):2094-2106. [17]GuanL, ZhaoX, TangL, et al., 2021. Thyroid transcription factor-1: structure, expression, function and its relationship with disease. Biomed Res Int, 2021:9957209. [18]HuangQM, ZengYM, LinHH, et al., 2017. Transfection with Livin and Survivin shRNA inhibits the growth and proliferation of non-small cell lung cancer cells. Mol Med Rep, 16(5):7086-7091. [19]IkedaK, Shaw-WhiteJR, WertSE, et al., 1996. Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells. Mol Cell Biol, 16(7):3626-3636. [20]KimJH, KimHS, KimBJ, et al., 2018. Prognostic impact of TTF-1 expression in non-squamous non-small-cell lung cancer: a meta-analysis. J Cancer, 9(22):4279-4286. [21]KizzireK, KharghariaS, RiceKG, 2013. High-affinity PEGylated polyacridine peptide polyplexes mediate potent in vivo gene expression. Gene Ther, 20(4):407-416. [22]Lara-GuerraH, RothJA, 2016. Gene therapy for lung cancer. Crit Rev Oncog, 21(1-2):115-124. [23]LeeAY, ChoMH, KimS, 2019. Recent advances in aerosol gene delivery systems using non-viral vectors for lung cancer therapy. Expert Opin Drug Deliv, 16(7):757-772. [24]LeiLY, ChenC, ZhaoJJ, et al., 2017. Targeted expression of miR-7 operated by TTF-1 promoter inhibited the growth of human lung cancer through the NDUFA4 pathway. Mol Ther Nucleic Acids, 6:183-197. [25]LiC, WuX, ZhangW, et al., 2014. AEG-1 promotes metastasis through downstream AKR1C2 and NF1 in liver cancer. Oncol Res, 22(4):203-211. [26]LiC, BrantE, BudakH, et al., 2021. CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(4):253-284. [27]LiJR, ZhengYJ, SunGY, et al., 2014. Restoration of miR-7 expression suppresses the growth of Lewis lung cancer cells by modulating epidermal growth factor receptor signaling. Oncol Rep, 32(6):2511-2516. [28]LiY, EggermontK, VanslembrouckV, et al., 2013. NKX2-1 activation by SMAD2 signaling after definitive endoderm differentiation in human embryonic stem cell. Stem Cells Dev, 22(9):1433-1442. [29]Linnerth-PetrikNM, SantryLA, YuDL, et al., 2012. Adeno-associated virus vector mediated expression of an oncogenic retroviral envelope protein induces lung adenocarcinomas in immunocompetent mice. PLoS ONE, 7(12):e51400. [30]LiuZL, JiangZM, HuangJY, et al., 2014. miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways. Int J Oncol, 44(5):1571-1580. [31]LuxCT, ScharenbergAM, 2017. Therapeutic gene editing safety and specificity. Hematol Oncol Clin North Am, 31(5):787-795. [32]MassaroG, HughesMP, WhalerSM, et al., 2020. Systemic AAV9 gene therapy using the synapsin I promoter rescues a mouse model of neuronopathic Gaucher disease but with limited cross-correction potential to astrocytes. Hum Mol Genet, 29(12):1933-1949. [33]NakazatoM, ChungHK, UlianichL, et al., 2000. Thyroglobulin repression of thyroid transcription factor 1 (TTF-1) gene expression is mediated by decreased DNA binding of nuclear factor I proteins which control constitutive TTF-1 expression. Mol Cell Biol, 20(22):8499-8512. [34]NaldiniL, 2015. Gene therapy returns to centre stage. Nature, 526(7573):351-360. [35]NasimF, SabathBF, EapenGA, 2019. Lung cancer. Med Clin North Am, 103(3):463-473. [36]PhilpottC, TovellH, FraylingIM, et al., 2017. The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics, 11:13. [37]PowellSK, Rivera-SotoR, GraySJ, 2015. Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy. Discov Med, 19(102):49-57. [38]PrullerJ, HoferI, GanassiM, et al., 2021. A human Myogenin promoter modified to be highly active in alveolar rhabdomyosarcoma drives an effective suicide gene therapy. Cancer Gene Ther, 28(5):427-441. [39]QianB, WangDM, GuXS, et al., 2018. LncRNA H19 serves as a ceRNA and participates in non-small cell lung cancer development by regulating microRNA-107. Eur Rev Med Pharmacol Sci, 22(18):5946-5953. [40]RaiKM, TakigawaN, ItoS, et al., 2011. Liposomal delivery of microRNA-7-expressing plasmid overcomes epidermal growth factor receptor tyrosine kinase inhibitor-resistance in lung cancer cells. Mol Cancer Ther, 10(9):1720-1727. [41]SebestyénMG, BudkerVG, BudkerT, et al., 2006. Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules. J Gene Med, 8(7):852-873. [42]SheikhS, ErnstD, KeatingA, 2021. Prodrugs and prodrug-activated systems in gene therapy. Mol Ther, 29(5):1716-1728. [43]SherYP, TzengTF, KanSF, et al., 2009. Cancer targeted gene therapy of BikDD inhibits orthotopic lung cancer growth and improves long-term survival. Oncogene, 28(37):3286-3295. [44]SuJC, RuanSL, DaiSK, et al., 2019. NF1 regulates apoptosis in ovarian cancer cells by targeting MCL1 via miR-142-5p. Pharmacogenomics, 20(3):155-165. [45]TolozaEM, MorseMA, LyerlyHK, 2006. Gene therapy for lung cancer. J Cell Biochem, 99(1):1-22. [46]UmakanthanS, BukeloMM, 2021. Concise genetic profile of lung carcinoma. Postgrad Med J, 0:1-5. [47]UmakanthanS, RaoAVC, MohammedW, 2021. Role of immunohistochemistry markers in neoplastic lung lesions. J Cancer Res Ther, 17(6):1382-1388. [48]WigginsJF, RuffinoL, KelnarK, et al., 2010. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res, 70(14):5923-5930. [49]WilsonC, NimickM, NehoffH, et al., 2017. ALK and IGF-1R as independent targets in crizotinib resistant lung cancer. Sci Rep, 7:13955. [50]XieXM, HsuJL, ChoiMG, et al., 2009. A novel hTERT promoter-driven E1A therapeutic for ovarian cancer. Mol Cancer Ther, 8(8):2375-2382. [51]XiongSD, ZhengYJ, JiangP, et al., 2011. MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2. Int J Biol Sci, 7(6):805-814. [52]ZhangBY, WangO, QinJC, et al., 2013. cis-Acting elements and trans-acting factors in the transcriptional regulation of Raf kinase inhibitory protein expression. PLoS ONE, 8(12):e83097. [53]ZhangEB, YinDD, SunM, et al., 2014. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis, 5(5):e1243. [54]ZhangR, WangQ, ZhangL, et al., 2015. Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B. Front Med, 9(1):90-99. [55]ZhaoJJ, WangKL, LiaoZY, et al., 2015. Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer. Mol Clin Oncol, 3(6):1329-1336. [56]ZhaoJJ, ChuFY, XuHL, et al., 2021. C/EBPα/miR-7 controls CD4+ T-cell activation and function and orchestrates experimental autoimmune hepatitis in mice. Hepatology, 74(1):379-396. [57]ZhaoX, YangJ, HuangRY, et al., 2021. The role and its mechanism of intermittent fasting in tumors: friend or foe? Cancer Biol Med, 18(1):63-73. [58]ZhuangXB, ZhaoC, LiJY, et al., 2019. Clinical features and therapeutic options in non-small cell lung cancer patients with concomitant mutations of EGFR, ALK, ROS1, KRAS or BRAF. Cancer Med, 8(6):2858-2866. Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou
310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE |
Open peer comments: Debate/Discuss/Question/Opinion
<1>