近年來，小分子核醣核酸 (microRNA) 被發現為抑癌基因的一種，而miR-125a-5p屬於其中之一。過去的研究中，miR-125a-5p被發現在多種腫瘤組織中的表現量相較於低。另一方面，存活素 (survivin) 過去也已經被證實會高表達於多種腫瘤組織中的致癌基因，且不存在於正常分化的組織，因此在許多的研究裡也說明高表現量的存活素會促進腫瘤生長，甚至影響癌症抗藥性以及癌症的轉移。
在本篇研究中，我們計畫結合基因療法與奈米科技，研發出能讓癌細胞自我啟動標靶miR-125a-5p訊息傳導路徑的抗癌藥物。首先，我們製作出帶有存活素啟動子 (survivin-promoter driven) 之miR-125a-5p質體(pSur-125a)，有趣的是，當我們使用微酯粒轉染法時，發現pSur-125a能在高表達存活素的癌細胞，包括MCF7分離出來具有非雌激素依賴型和泰莫西芬抗藥性的MCF7-TamC3乳癌細胞、KB分離出來具有多重抗藥性和紫杉醇抗藥性的KB-TAX50子宮頸癌細胞、以及NTUB1分離出來具有多重抗藥性和紫杉醇抗藥性的NTU0.017膀胱癌細胞中顯著地降低其細胞存活率；但不會影響沒有表達存活素的正常細胞之存活率。我們也在更進一步的功能性分析發現，實驗中以微酯粒轉染pSur-125a，確實會使細胞表達更多miR-125a-5p，並同時抑制HDAC5、Sp1和HER2，已知這些蛋白會受miR-125a-5p的調控抑制進而導致癌細胞凋亡。同時，我們進一步研發出能攜帶pSur-125a的奈米粒子。此奈米粒子之生物化學特性包括大小、型態以及介面電位也在本篇研究中被測試。特別的是，N-pSur-125a不需使用任何轉染試劑，也能與微酯粒轉染pSur-125同樣使pSur-125進到癌細胞中。此奈米粒子在癌細胞中的調控機轉，同樣是透過標靶miR-125a-5p訊息傳導路徑，在有表達存活素、且不論是否有多重抗藥性的癌細胞中降低了細胞存活率；有趣的是，N-pSur-125a不會影響沒有表達存活素的正常細胞之存活率，證實了N-pSur-125a能專一性的標靶表達存活素的癌細胞。在本篇研究裡，我們所研發出新穎的奈米藥物N-pSur-125a能作用於表達存活素的癌細胞中進一步誘發細胞凋亡。我們相信，未來N-pSur-125a 在癌症治療上是極具潛力並且值得更深入的研究探討。

The microRNA, miR-125a-5p, is a recently discovered tumor suppressor and downregulation of miR-125a-5p has been found in a variety types of tumor. In contrast, survivin is a well-known oncogene highly expressed in most tumor tissues, but not in the differentiated normal tissues. Moreover, upregulation of survivin has widely been demonstrated to promote tumor cells’ survival, drug resistance and metastasis. In the current study, by combining gene therapy and nanotechnology, we aim to develop a novel “cancer cells self-activating” and “multi-oncogenic pathway-targeting” therapeutic agent for cancer therapy.
A survivin-promoter driven miR-125a-5p expressing plasmid DNA (pSur-125a) was created. Liposomal delivery of pSur-125a significantly decreased the cell viability of a variety survivin positive cancer cells including the human MCF7-dervided estrogen-independent and tamoxifen cross-resistant MCF7-TamC3 breast cancer cells, the KB-derived MDR-1/P-gp (multi-drug resistance-1) expressing paclitaxel-resistant KB-TAX50 cervical cancer cells, and the NTUB1-derived MDR-1 expressing paclitaxel-resistant NTU0.017 bladder cancer cells, but spared the survivin non-expressing normal cells. Further functional analysis showed that liposomal delivery of pSur-125a induced the overexpression of miR-125a-5p, downregulated the expression of HDAC5, Sp1 and HER2 which are known molecular targets of miR-125a-5p, and promoted apoptosis in the treated cancer cells.
The p-Sur-125a plasmid DNA encapsulated nanoparticle (N-pSur-125a) was subsequently created. The biophysical properties such as size, morphology, and zeta potential of N-pSur-125a were examined. Similar to the liposomal delivery of pSur-125a, the nanodrug N-pSur-125a, without the use of any transfection reagent, was capable of delivering the “therapeutic core” pSur-125a and overexpressing miR-125a-5p in cancer cells. N-pSur-125a decreased the cell viability of different survivin-expressing, MDR1-expressing/non-expressing cancer cells via multi-oncogenic pathways-targeting in vitro. Notably, N-pSur-125a only exhibited minimal effects on cell viability in survivin non-expressing normal cells, supporting that N-pSur-125a is survivin-expressing cancer cells specific.
In conclusion, the newly created N-pSur-125a is functional in inducing apoptosis in survivin-expressing cancer cells. N-pSur-125a has the potential for treating cancers and it also warrants further investigations.

Ambrosini, G., Adida, C., & Altieri, D. C. (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med, 3(8), 917-921. doi:10.1038/nm0897-917
Anandharaj, A., Cinghu, S., & Park, W. Y. (2011). Rapamycin-mediated mTOR inhibition attenuates survivin and sensitizes glioblastoma cells to radiation therapy. Acta Biochim Biophys Sin (Shanghai), 43(4), 292-300. doi:10.1093/abbs/gmr012
Arias, L. S., Pessan, J. P., Vieira, A. P. M., Lima, T. M. T., Delbem, A. C. B., & Monteiro, D. R. (2018). Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity. Antibiotics (Basel), 7(2). doi:10.3390/antibiotics7020046
Banerjee, S., Cui, H., Xie, N., Tan, Z., Yang, S., Icyuz, M., . . . Liu, G. (2013). miR-125a-5p regulates differential activation of macrophages and inflammation. J Biol Chem, 288(49), 35428-35436. doi:10.1074/jbc.M112.426866
Benedetti, R., Conte, M., & Altucci, L. (2015). Targeting Histone Deacetylases in Diseases: Where Are We? Antioxid Redox Signal, 23(1), 99-126. doi:10.1089/ars.2013.5776
Bobo, D., Robinson, K. J., Islam, J., Thurecht, K. J., & Corrie, S. R. (2016). Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm Res, 33(10), 2373-2387. doi:10.1007/s11095-016-1958-5
Cai, X., Zhu, Q., Zeng, Y., Zeng, Q., Chen, X., & Zhan, Y. (2019). Manganese Oxide Nanoparticles As MRI Contrast Agents In Tumor Multimodal Imaging And Therapy. Int J Nanomedicine, 14, 8321-8344. doi:10.2147/ijn.S218085
Cai, Y., Ma, W., Huang, X., Cao, L., Li, H., Jiang, Y., . . . Yin, Y. (2015). Effect of survivin on tumor growth of colorectal cancer in vivo. Int J Clin Exp Pathol, 8(10), 13267-13272.
Cai, Z., Li, J., Zhuang, Q., Zhang, X., Yuan, A., Shen, L., . . . Shen, J. (2018). MiR-125a-5p ameliorates monocrotaline-induced pulmonary arterial hypertension by targeting the TGF-β1 and IL-6/STAT3 signaling pathways. Exp Mol Med, 50(4), 45. doi:10.1038/s12276-018-0068-3
Cao, Y., Shen, T., Zhang, C., Zhang, Q. H., & Zhang, Z. Q. (2019). MiR-125a-5p inhibits EMT of ovarian cancer cells by regulating TAZ/EGFR signaling pathway. Eur Rev Med Pharmacol Sci, 23(19), 8249-8256. doi:10.26355/eurrev_201910_19134
Cardoso, M. M., Peça, I. N., & Roque, A. C. (2012). Antibody-conjugated nanoparticles for therapeutic applications. Curr Med Chem, 19(19), 3103-3127. doi:10.2174/092986712800784667
Carter, B. Z., Mak, D. H., Schober, W. D., Cabreira-Hansen, M., Beran, M., McQueen, T., . . . Andreeff, M. (2006). Regulation of survivin expression through Bcr-Abl/MAPK cascade: targeting survivin overcomes imatinib resistance and increases imatinib sensitivity in imatinib-responsive CML cells. Blood, 107(4), 1555-1563. doi:10.1182/blood-2004-12-4704
Chelobanov, B. P., Repkova, M. N., Baiborodin, S. I., Ryabchikova, E. I., & Stetsenko, D. A. (2017). [Nuclear delivery of oligonucleotides via nanocomposites based on TiO2 nanoparticles and polylysine]. Mol Biol (Mosk), 51(5), 797-808. doi:10.7868/s0026898417050068
Cheng, K. Y., Wang, Z. L., Gu, Q. Y., & Hao, M. (2016). Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma: A Meta-Analysis. PLoS One, 11(10), e0165117. doi:10.1371/journal.pone.0165117
Chew, H. K. (2001). Adjuvant therapy for breast cancer: who should get what? West J Med, 174(4), 284-287. doi:10.1136/ewjm.174.4.284
de la Torre, C., Domínguez-Berrocal, L., Murguía, J. R., Marcos, M. D., Martínez-Máñez, R., Bravo, J., & Sancenón, F. (2018). ϵ-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells. Chemistry, 24(8), 1890-1897. doi:10.1002/chem.201704161
DeVita, V. T., Jr., & Rosenberg, S. A. (2012). Two hundred years of cancer research. N Engl J Med, 366(23), 2207-2214. doi:10.1056/NEJMra1204479
Elmore, S. (2007). Apoptosis: a review of programmed cell death. Toxicol Pathol, 35(4), 495-516. doi:10.1080/01926230701320337
Fulda, S., & Debatin, K. M. (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25(34), 4798-4811. doi:10.1038/sj.onc.1209608
Griffith, T. S., Stokes, B., Kucaba, T. A., Earel, J. K., Jr., VanOosten, R. L., Brincks, E. L., & Norian, L. A. (2009). TRAIL gene therapy: from preclinical development to clinical application. Curr Gene Ther, 9(1), 9-19. doi:10.2174/156652309787354612
Gu, Y., Jin, S., Wang, F., Hua, Y., Yang, L., Shu, Y., . . . Guo, R. (2014). Clinicopathological significance of PI3K, Akt and survivin expression in gastric cancer. Biomed Pharmacother, 68(4), 471-475. doi:10.1016/j.biopha.2014.03.010
Hacein-Bey-Abina, S., Hauer, J., Lim, A., Picard, C., Wang, G. P., Berry, C. C., . . . Cavazzana-Calvo, M. (2010). Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med, 363(4), 355-364. doi:10.1056/NEJMoa1000164
Hoshyar, N., Gray, S., Han, H., & Bao, G. (2016). The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine (Lond), 11(6), 673-692. doi:10.2217/nnm.16.5
Hsieh, T. H., Hsu, C. Y., Tsai, C. F., Long, C. Y., Wu, C. H., Wu, D. C., . . . Tsai, E. M. (2015). HDAC inhibitors target HDAC5, upregulate microRNA-125a-5p, and induce apoptosis in breast cancer cells. Mol Ther, 23(4), 656-666. doi:10.1038/mt.2014.247
Huang, J., Bu, L., Xie, J., Chen, K., Cheng, Z., Li, X., & Chen, X. (2010). Effects of nanoparticle size on cellular uptake and liver MRI with polyvinylpyrrolidone-coated iron oxide nanoparticles. ACS Nano, 4(12), 7151-7160. doi:10.1021/nn101643u
Huang, J., Lyu, H., Wang, J., & Liu, B. (2015). MicroRNA regulation and therapeutic targeting of survivin in cancer. Am J Cancer Res, 5(1), 20-31.
Huang, W. T., Tsai, Y. H., Chen, S. H., Kuo, C. W., Kuo, Y. L., Lee, K. T., . . . Cheung, C. H. A. (2017). HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells. Front Pharmacol, 8, 902. doi:10.3389/fphar.2017.00902
Iwai, M., Minematsu, T., Li, Q., Iwatsubo, T., & Usui, T. (2011). Utility of P-glycoprotein (MDR1/ABCB1/P-gp) and Organic Cation Transporter 1 (OCT1) Double-transfected LLC-PK1 Cells for Studying the Interaction of YM155 Monobromide, a Novel Small Molecule Survivin Suppressant, with MDR1. Drug Metabolism and Disposition, dmd.111.040733. doi:10.1124/dmd.111.040733
Jaiswal, P. K., Goel, A., & Mittal, R. D. (2015). Survivin: A molecular biomarker in cancer. Indian J Med Res, 141(4), 389-397. doi:10.4103/0971-5916.159250
Jiang, W., Kim, B. Y., Rutka, J. T., & Chan, W. C. (2008). Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol, 3(3), 145-150. doi:10.1038/nnano.2008.30
Kaczanowski, S. (2016). Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol, 13(3), 031001. doi:10.1088/1478-3975/13/3/031001
Kelly, R. J., Thomas, A., Rajan, A., Chun, G., Lopez-Chavez, A., Szabo, E., . . . Giaccone, G. (2013). A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Ann Oncol, 24(10), 2601-2606. doi:10.1093/annonc/mdt249
Kinner, A., Wu, W., Staudt, C., & Iliakis, G. (2008). Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res, 36(17), 5678-5694. doi:10.1093/nar/gkn550
Kiwaki, K., & Matsuda, I. (1996). Gene therapy for ornithine transcarbamylase deficiency. Acta Paediatr Jpn, 38(2), 189-192. doi:10.1111/j.1442-200x.1996.tb03467.x
Kulkarni, S. A., & Feng, S. S. (2013). Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery. Pharm Res, 30(10), 2512-2522. doi:10.1007/s11095-012-0958-3
Kusner, L. L., Ciesielski, M. J., Marx, A., Kaminski, H. J., & Fenstermaker, R. A. (2014). Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study. PLoS One, 9(7), e102231. doi:10.1371/journal.pone.0102231
Leung, E., Kannan, N., Krissansen, G. W., Findlay, M. P., & Baguley, B. C. (2010). MCF-7 breast cancer cells selected for tamoxifen resistance acquire new phenotypes differing in DNA content, phospho-HER2 and PAX2 expression, and rapamycin sensitivity. Cancer Biol Ther, 9(9), 717-724. doi:10.4161/cbt.9.9.11432
Lewis, K. D., Samlowski, W., Ward, J., Catlett, J., Cranmer, L., Kirkwood, J., . . . Gonzalez, R. (2011). A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma. Invest New Drugs, 29(1), 161-166. doi:10.1007/s10637-009-9333-6
Li, F., Ambrosini, G., Chu, E. Y., Plescia, J., Tognin, S., Marchisio, P. C., & Altieri, D. C. (1998). Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 396(6711), 580-584. doi:10.1038/25141
Li, Z., Xiang, J., Zhang, W., Fan, S., Wu, M., Li, X., & Li, G. (2009). Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model. Cancer Gene Ther, 16(5), 423-429. doi:10.1038/cgt.2008.97
Li, Z., Zhang, L., Tang, C., & Yin, C. (2017). Co-Delivery of Doxorubicin and Survivin shRNA-Expressing Plasmid Via Microenvironment-Responsive Dendritic Mesoporous Silica Nanoparticles for Synergistic Cancer Therapy. Pharm Res, 34(12), 2829-2841. doi:10.1007/s11095-017-2264-6
Lim, H. J., & Ledger, W. (2016). Targeted therapy in ovarian cancer. Womens Health (Lond), 12(3), 363-378. doi:10.2217/whe.16.4
Lin, K. Y., Cheng, S. M., Tsai, S. L., Tsai, J. Y., Lin, C. H., & Cheung, C. H. (2016). Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study. Onco Targets Ther, 9, 2601-2613. doi:10.2147/ott.S101209
Liu, H., Ma, Y., Liu, C., Li, P., & Yu, T. (2018). Reduced miR-125a-5p level in non-small-cell lung cancer is associated with tumour progression. Open Biol, 8(10). doi:10.1098/rsob.180118
Lánczky, A., Nagy, Á., Bottai, G., Munkácsy, G., Szabó, A., Santarpia, L., & Győrffy, B. (2016). miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat, 160(3), 439-446. doi:10.1007/s10549-016-4013-7
Malinowsky, K., Wolff, C., Gündisch, S., Berg, D., & Becker, K. (2010). Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues. J Cancer, 2, 26-35. doi:10.7150/jca.2.26
Mandal, H., Katiyar, S. S., Swami, R., Kushwah, V., Katare, P. B., Kumar Meka, A., . . . Jain, S. (2018). ε-Poly-l-Lysine/plasmid DNA nanoplexes for efficient gene delivery in vivo. Int J Pharm, 542(1-2), 142-152. doi:10.1016/j.ijpharm.2018.03.021
Mann, A., Richa, R., & Ganguli, M. (2008). DNA condensation by poly-L-lysine at the single molecule level: role of DNA concentration and polymer length. J Control Release, 125(3), 252-262. doi:10.1016/j.jconrel.2007.10.019
Martínez-García, D., Manero-Rupérez, N., Quesada, R., Korrodi-Gregório, L., & Soto-Cerrato, V. (2019). Therapeutic strategies involving survivin inhibition in cancer. Med Res Rev, 39(3), 887-909. doi:10.1002/med.21547
Morales, J., Li, L., Fattah, F. J., Dong, Y., Bey, E. A., Patel, M., . . . Boothman, D. A. (2014). Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr, 24(1), 15-28. doi:10.1615/critreveukaryotgeneexpr.2013006875
Moreb, J. S. (2019). Off-target effects of carfilzomib that cause cardiotoxicity. Blood, 133(7), 626-628. doi:10.1182/blood-2018-12-889758
Nakahara, T., Kita, A., Yamanaka, K., Mori, M., Amino, N., Takeuchi, M., . . . Sasamata, M. (2007). YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res, 67(17), 8014-8021. doi:10.1158/0008-5472.Can-07-1343
Nakahara, T., Kita, A., Yamanaka, K., Mori, M., Amino, N., Takeuchi, M., . . . Sasamata, M. (2011). Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci, 102(3), 614-621. doi:10.1111/j.1349-7006.2010.01834.x
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne), 9, 402. doi:10.3389/fendo.2018.00402
Peng, Y., & Croce, C. M. (2016). The role of MicroRNAs in human cancer. Signal Transduct Target Ther, 1, 15004. doi:10.1038/sigtrans.2015.4
Pohlmann, P. R., Mayer, I. A., & Mernaugh, R. (2009). Resistance to Trastuzumab in Breast Cancer. Clin Cancer Res, 15(24), 7479-7491. doi:10.1158/1078-0432.Ccr-09-0636
Qin, X., Wan, Y., Wang, S., & Xue, M. (2016). MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2. Drug Des Devel Ther, 10, 71-79. doi:10.2147/dddt.S93104
Ramos, P., & Bentires-Alj, M. (2015). Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene, 34(28), 3617-3626. doi:10.1038/onc.2014.314
Rationalizing combination therapies. (2017). Nat Med, 23(10), 1113. doi:10.1038/nm.4426
Schwenk, M. H. (2010). Ferumoxytol: a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. Pharmacotherapy, 30(1), 70-79. doi:10.1592/phco.30.1.70
Sehara, Y., Sawicka, K., Hwang, J. Y., Latuszek-Barrantes, A., Etgen, A. M., & Zukin, R. S. (2013). Survivin Is a transcriptional target of STAT3 critical to estradiol neuroprotection in global ischemia. J Neurosci, 33(30), 12364-12374. doi:10.1523/jneurosci.1852-13.2013
Shin, S., Sung, B. J., Cho, Y. S., Kim, H. J., Ha, N. C., Hwang, J. I., . . . Oh, B. H. (2001). An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 40(4), 1117-1123. doi:10.1021/bi001603q
Stein, C. J., & Colditz, G. A. (2004). Modifiable risk factors for cancer. British Journal of Cancer, 90(2), 299-303. doi:10.1038/sj.bjc.6601509
Su, C.-H., & Cheng, F.-Y. (2015). In vitro and in vivo applications of alginate/iron oxide nanocomposites for theranostic molecular imaging in a brain tumor model. RSC Advances, 5(109), 90061-90064. doi:10.1039/C5RA20723A
Su, C. H., Tsai, C. Y., Tomanek, B., Chen, W. Y., & Cheng, F. Y. (2016). Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma theranostics applications. Nanoscale, 8(15), 7866-7870. doi:10.1039/c6nr00280c
Sun, L., Lian, J. X., & Meng, S. (2019). MiR-125a-5p promotes osteoclastogenesis by targeting TNFRSF1B. Cell Mol Biol Lett, 24, 23. doi:10.1186/s11658-019-0146-0
Talekar, M., Trivedi, M., Shah, P., Ouyang, Q., Oka, A., Gandham, S., & Amiji, M. M. (2016). Combination wt-p53 and MicroRNA-125b Transfection in a Genetically Engineered Lung Cancer Model Using Dual CD44/EGFR-targeting Nanoparticles. Mol Ther, 24(4), 759-769. doi:10.1038/mt.2015.225
Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017). GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 45(W1), W98-w102. doi:10.1093/nar/gkx247
Tiedt, S., Prestel, M., Malik, R., Schieferdecker, N., Duering, M., Kautzky, V., . . . Dichgans, M. (2017). RNA-Seq Identifies Circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as Potential Biomarkers for Acute Ischemic Stroke. Circ Res, 121(8), 970-980. doi:10.1161/circresaha.117.311572
Trujillo-Alonso, V., Pratt, E. C., Zong, H., Lara-Martinez, A., Kaittanis, C., Rabie, M. O., . . . Guzman, M. L. (2019). FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels. Nat Nanotechnol, 14(6), 616-622. doi:10.1038/s41565-019-0406-1
Vo, D. T., Karanam, N. K., Ding, L., Saha, D., Yordy, J. S., Giri, U., . . . Story, M. D. (2019). miR-125a-5p Functions as Tumor Suppressor microRNA And Is a Marker of Locoregional Recurrence And Poor prognosis in Head And Neck Cancer. Neoplasia, 21(9), 849-862. doi:10.1016/j.neo.2019.06.004
Wang, X. H., Yu, Y. X., Cheng, K., Yang, W., Liu, Y. A., & Peng, H. S. (2019). Polylysine modified conjugated polymer nanoparticles loaded with the singlet oxygen probe 1,3-diphenylisobenzofuran and the photosensitizer indocyanine green for use in fluorometric sensing and in photodynamic therapy. Mikrochim Acta, 186(12), 842. doi:10.1007/s00604-019-3924-5
Wheatley, S. P., & Altieri, D. C. (2019). Survivin at a glance. J Cell Sci, 132(7). doi:10.1242/jcs.223826
Wightman, B., Ha, I., & Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75(5), 855-862. doi:10.1016/0092-8674(93)90530-4
Wilson, T. R., Johnston, P. G., & Longley, D. B. (2009). Anti-apoptotic mechanisms of drug resistance in cancer. Curr Cancer Drug Targets, 9(3), 307-319. doi:10.2174/156800909788166547
Xiang, J. J., Tang, J. Q., Zhu, S. G., Nie, X. M., Lu, H. B., Shen, S. R., . . . Li, G. Y. (2003). IONP-PLL: a novel non-viral vector for efficient gene delivery. J Gene Med, 5(9), 803-817. doi:10.1002/jgm.419
Xu, L., Li, Y., Yin, L., Qi, Y., Sun, H., Sun, P., . . . Peng, J. (2018). miR-125a-5p ameliorates hepatic glycolipid metabolism disorder in type 2 diabetes mellitus through targeting of STAT3. Theranostics, 8(20), 5593-5609. doi:10.7150/thno.27425
Xu, X., Tao, Y., Niu, Y., Wang, Z., Zhang, C., Yu, Y., & Ma, L. (2019). miR-125a-5p inhibits tumorigenesis in hepatocellular carcinoma. Aging (Albany NY), 11(18), 7639-7662. doi:10.18632/aging.102276
Yang, X., Qiu, J., Kang, H., Wang, Y., & Qian, J. (2018). miR-125a-5p suppresses colorectal cancer progression by targeting VEGFA. Cancer Manag Res, 10, 5839-5853. doi:10.2147/cmar.S161990
Ye, H., Zhu, W., Mei, L., & Lu, Z. (2019). Prognostic and clinicopathologic significance of MicroRNA-125a-5p in cancers: A meta-analysis. Medicine (Baltimore), 98(31), e16685. doi:10.1097/md.0000000000016685
Yi, R., & Fuchs, E. (2011). MicroRNAs and their roles in mammalian stem cells. J Cell Sci, 124(Pt 11), 1775-1783. doi:10.1242/jcs.069104
Yu, C., Hu, Y., Duan, J., Yuan, W., Wang, C., Xu, H., & Yang, X. D. (2011). Novel aptamer-nanoparticle bioconjugates enhances delivery of anticancer drug to MUC1-positive cancer cells in vitro. PLoS One, 6(9), e24077. doi:10.1371/journal.pone.0024077
Zhang, D., Guo, H., Feng, W., & Qiu, H. (2019). LAMC2 regulated by microRNA-125a-5p accelerates the progression of ovarian cancer via activating p38 MAPK signalling. Life Sci, 232, 116648. doi:10.1016/j.lfs.2019.116648
Zhang, X., Liu, J., Li, X., Li, F., Lee, R. J., Sun, F., . . . Teng, L. (2019). Trastuzumab-Coated Nanoparticles Loaded With Docetaxel for Breast Cancer Therapy. Dose Response, 17(3), 1559325819872583. doi:10.1177/1559325819872583
Zhu, H., Zhang, G., Wang, Y., Xu, N., He, S., Zhang, W., . . . Xu, N. (2010). Inhibition of ErbB2 by Herceptin reduces survivin expression via the ErbB2-beta-catenin/TCF4-survivin pathway in ErbB2-overexpressed breast cancer cells. Cancer Sci, 101(5), 1156-1162. doi:10.1111/j.1349-7006.2010.01528.x