Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector
Multiple proteins are involved in network regulation through the crosstalk of different signaling pathways in cancers. Here, we propose a novel strategy of genome therapy with branch-PCR-assembled gene nanovectors to perform network-based gene regulation at multiple levels for cancer therapy. To val...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/20/6943 |
| _version_ | 1827648579394600960 |
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| author | Longhuai Cheng Liqing Lu Ziyi Chen Dejun Ma Zhen Xi |
| author_facet | Longhuai Cheng Liqing Lu Ziyi Chen Dejun Ma Zhen Xi |
| author_sort | Longhuai Cheng |
| collection | DOAJ |
| description | Multiple proteins are involved in network regulation through the crosstalk of different signaling pathways in cancers. Here, we propose a novel strategy of genome therapy with branch-PCR-assembled gene nanovectors to perform network-based gene regulation at multiple levels for cancer therapy. To validate network-based multiplex-gene regulation for genome therapy, we chose to simultaneously target one tumor suppressor gene (<i>TP53</i>) and one oncogene (<i>MYC</i>) in two different signaling pathways. The results showed that, compared to gene nanovectors targeting single genes (NP-TP53 and NP-shMYC), branch-PCR-assembled gene nanovectors simultaneously expressing p53 proteins and MYC shRNA arrays (NP-TP53-shMYC) showed enhanced antitumor efficacy in both MDA-MB-231 cancer cells and an MDA-MB-231-tumor-bearing mouse model. These findings indicate the feasibility and effectiveness of genome therapy in cancer therapy. |
| first_indexed | 2024-03-09T19:42:08Z |
| format | Article |
| id | doaj.art-29a585ebe45847d7ad4439f445d42603 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:42:08Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-29a585ebe45847d7ad4439f445d426032023-11-24T01:34:19ZengMDPI AGMolecules1420-30492022-10-012720694310.3390/molecules27206943Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene NanovectorLonghuai Cheng0Liqing Lu1Ziyi Chen2Dejun Ma3Zhen Xi4State Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, National Pesticide Engineering Research Center, Collaborative Innovation Center of Chemical Science and Engineering, College of Chemistry, Nankai University, Tianjin 300071, ChinaMultiple proteins are involved in network regulation through the crosstalk of different signaling pathways in cancers. Here, we propose a novel strategy of genome therapy with branch-PCR-assembled gene nanovectors to perform network-based gene regulation at multiple levels for cancer therapy. To validate network-based multiplex-gene regulation for genome therapy, we chose to simultaneously target one tumor suppressor gene (<i>TP53</i>) and one oncogene (<i>MYC</i>) in two different signaling pathways. The results showed that, compared to gene nanovectors targeting single genes (NP-TP53 and NP-shMYC), branch-PCR-assembled gene nanovectors simultaneously expressing p53 proteins and MYC shRNA arrays (NP-TP53-shMYC) showed enhanced antitumor efficacy in both MDA-MB-231 cancer cells and an MDA-MB-231-tumor-bearing mouse model. These findings indicate the feasibility and effectiveness of genome therapy in cancer therapy.https://www.mdpi.com/1420-3049/27/20/6943branch-PCRgene therapyTP53MYCgenome therapycancer therapy |
| spellingShingle | Longhuai Cheng Liqing Lu Ziyi Chen Dejun Ma Zhen Xi Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector Molecules branch-PCR gene therapy TP53 MYC genome therapy cancer therapy |
| title | Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector |
| title_full | Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector |
| title_fullStr | Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector |
| title_full_unstemmed | Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector |
| title_short | Multiple-Gene Regulation for Enhanced Antitumor Efficacy with Branch-PCR-Assembled TP53 and MYC Gene Nanovector |
| title_sort | multiple gene regulation for enhanced antitumor efficacy with branch pcr assembled tp53 and myc gene nanovector |
| topic | branch-PCR gene therapy TP53 MYC genome therapy cancer therapy |
| url | https://www.mdpi.com/1420-3049/27/20/6943 |
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