Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells

Qin, Tao; Ma, Wei; Liu, Shanxi; Yang, Guangxiao; Wang, Quanying; Zhao, Xinhan

doi:10.3892/mmr.2010.343

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…We design the BDNF-HA2TAT/AAV, and have it produced by Dr. Guang-xiao Yang as a previously reported with modification 28 . The AAV used in our present study are based on serotype 2.…”

Section: Methodsmentioning

confidence: 99%

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder

Liu

Jiang

et al. 2016

Sci Rep

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Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.

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“…We design the BDNF-HA2TAT/AAV, and have it produced by Dr. Guang-xiao Yang as a previously reported with modification 28 . The AAV used in our present study are based on serotype 2.…”

Section: Methodsmentioning

confidence: 99%

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder

Liu

Jiang

et al. 2016

Sci Rep

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“…Decelerated Par-4 levels have been reported in several types of cancers; various strategies have been suggested and tested to restore its apoptosis-inducing levels in cancer cells. In in vivo settings, Par-4 levels have been augmented using the adenoviral Par-4 constructs as well as by nano-liposomal delivery of Par-4 constructs [ 48 ]. Diverse natural/semi-synthetic pharmacophores have been explored for their Par-4-inducing properties.…”

Section: Discussionmentioning

confidence: 99%

Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells

Katoch

Jamwal

Faheem

et al. 2021

Translational Oncology

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The last decade has witnessed a substantial expansion in the field of microRNA (miRNA) biology, providing crucial insights into the role of miRNAs in disease pathology, predominantly in cancer progression and its metastatic spread. The discovery of tumor-suppressing miRNAs represents a potential approach for developing novel therapeutics. In this context, through miRNA microarray analysis, we examined the consequences of Prostate apoptosis response-4 (Par-4), a well-established tumor-suppressor, stimulation on expression of different miRNAs in Panc-1 cells. The results strikingly indicated elevated miR-200c levels in these cells upon Par-4 overexpression. Intriguingly, the Reverse Phase Protein Array (RPPA) analysis revealed differentially expressed proteins (DEPs), which overlap between miR200c- and Par-4-transfected cells, highlighting the cross-talks between these pathways. Notably, Phospho-p44/42 MAPK; Bim; Bcl-xL; Rb Phospho-Ser807, Ser811; Akt Phospho-Ser473; Smad1/5 Phospho-Ser463/Ser465 and Zyxin scored the most significant DEPs among the two data sets. Furthermore, the GFP-Par-4-transfected cells depicted an impeded expression of critical mesenchymal markers viz. TGF-β1, TGF-β2, ZEB-1, and Twist-1, concomitant with augmented miR-200c and E-cadherin levels. Strikingly, while Par-4 overexpression halted ZEB-1 at the transcriptional level; contrarily, silencing of endogenous Par-4 by siRNA robustly augmented the Epithelial-mesenchymal transition (EMT) markers, along with declining miR-200c levels. The pharmacological Par-4-inducer, NGD16, triggered Par-4 expression which corresponded with increased miR-200c resulting in the ZEB-1 downregulation. Noteworthily, tumor samples obtained from the syngenic mouse pancreatic cancer model revealed elevated miR-200c levels in the NGD16-treated mice that positively correlated with the Par-4 and E-cadherin levels in vivo ; while a negative correlation was evident with ZEB-1 and Vimentin.

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“…Prostate apoptosis response-4 (Par-4) is the tumor-suppressor protein that results in the cell apoptosis in tumor cells not in normal cells. A study showed that expression of AAV/Par-4 induced rapid cell death in the HepG2 hepatocarcinoma model [86]. …”

Section: Advances In Aav-mediated Cancer Gene Therapymentioning

confidence: 99%

Adeno-associated virus-mediated cancer gene therapy: Current status

Luo

Sun

et al. 2015

Cancer Letters

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Gene therapy is one of the frontiers of modern medicine. Adeno-associated virus (AAV)-mediated gene therapy is becoming a promising approach to treat a variety of diseases and cancers. AAV-mediated cancer gene therapies have rapidly advanced due to their superiority to other gene-carrying vectors, such as the lack of pathogenicity, the ability to transfect both dividing and non-dividing cells, low host immune response, and long-term expression. This article reviews and provides up to date knowledge on AAV-mediated cancer gene therapy.

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Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells

Cited by 4 publications

References 19 publications

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder

Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells

Adeno-associated virus-mediated cancer gene therapy: Current status

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