Silencing of Inducible Immunoproteasome Subunit Expression by Chemically Modified siRNA and shRNA

Gvozdeva, Olga V.; Prassolov, Vladimir; Zenkova, Marina A.; Vlassov, Valentin V.; Chernolovskaya, E. L.

doi:10.1080/15257770.2016.1184275

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…When entering a cell, the hairpin sequence can be automatically processed into siRNAs, which enable target gene silencing. Therefore, loading the carrier of the shRNA can be passed to the progeny cells so that the silencing of genes can be inherited ( 19 , 20 ). Lentivirus can infect both mitotic and non-mitotic cells, and the RNA interference sequence that it carries can be randomly inserted and integrated into the genome of the host cell for long-term expression ( 21 , 22 ).…”

Section: Discussionmentioning

confidence: 99%

Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF‑7 cells inï¿½vitro and inï¿½vivo and its mechanism of action

Meng

Zhang

et al. 2018

Oncol Rep

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A disintegrin and metalloprotease 17 (ADAM17) is highly expressed in many malignant tumors and is closely related to their development. We showed in a previous study that silencing of ADAM17 by siRNA inhibited the growth of MCF-7 breast cancer cells in vitro and in vivo. In the present study, we investigated the effects of ADAM17-short hairpin RNA (ADAM17-shRNA) on MCF-7 breast cancer cells and explored the potential action pathway. In vitro, transfection of shRNAs was performed using a lentivirus, and the effects of ADAM17-shRNA on invasion, proliferation and cell cycle distribution of MCF-7 cells were assessed by Boyden chamber method, real-time cell analysis and flow cytometry, respectively. In vivo, MCF-7 cells with different administrations were transplanted subcutaneously into nude mice, and the effect of ADAM17-shRNA on the growth of transplanted tumors was assessed. In addition, the morphological structures were observed by H&E staining, and the expression of ADAM17 and Ki-67 was assessed by immunohistochemistry; expression of ADAM17, EGFR, p-EGFR, AKT, p-AKT, ERK and p-ERK proteins was assessed by western blotting, respectively. Our data showed that ADAM17-shRNA successfully inhibited ADAM17 mRNA expression, invasion and proliferation of MCF-7 cells resulting in G0/G1 phase arrest, and significantly inhibited the growth of transplanted tumors with larger areas of necrosis, low expression of ADAM17 and Ki-67 and reduced protein expression of ADAM17, EGFR, p-EGFR, AKT, p-AKT, ERK, and p-ERK in the tumor tissues. The present research suggests that ADAM17-shRNA can inhibit MCF-7 cell invasion and proliferation in vitro and inhibit MCF-7 xenograft growth in vivo through the EGFR/PI3K/AKT and EGFR/MEK/ERK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF‑7 cells inï¿½vitro and inï¿½vivo and its mechanism of action

Meng

Zhang

et al. 2018

Oncol Rep

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“…Short hairpin RNA (shRNA) is a stem-loop RNA that also silences a specific gene via RNAi (Lam et al., 2015 ). Compared with siRNA, it provides long-lasting gene silencing and comparable efficiency (Gvozdeva et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer

Hong

Zhang

et al. 2018

Drug Delivery

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The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.

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Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles (‘vehicular smog’)

Pomatto

Cline

Woodward

et al. 2018

Free Radical Biology and Medicine

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Environmental toxicants are catalysts for protein damage, aggregation, and the aging process. Fortunately, evolution selected adaptive homeostasis as a system to mitigate such damage by expanding the normal capacity to cope with toxic stresses. Little is known about the subcellular degradative responses to proteins oxidatively damaged by air pollution. To better understand the impact of environmental toxicants upon the adaptive homeostatic response, female C57BL/6 mice were exposed for 10 weeks to filtered air or reaerosolized vehicular-derived nano-scale particulate matter (nPM), at which point tissues from young (6 month) and middle-aged (21 month) mice were studied. We found significant increases of proteolytic capacity in lung, liver, and heart. Up to two-fold increases were seen in the 20S Proteasome, the Immunoproteasome, the mitochondrial Lon protease, and NF-E2-related factor 2 (Nrf2), a major transcriptional factor for these and other stress-responsive genes. The responses were equivalent in all organs, despite the indirect input of inhaled particles to heart and liver which are downstream of lung. To our knowledge, this is the first exploration of proteostatic responses to oxidative damage by air pollution. Although, middle-aged mice had higher basal levels, their Nrf2-responsive-genes exhibited no response to nanoparticulate exposure. We also found a parallel age-associated rise in the Nrf2 transcriptional inhibitors, Bach1 and c-Myc which appear to attenuate adaptive responses in older mammals, possibly explaining the 'age-ceiling effect.' This report extends prior findings in male mice by demonstrating the involvement of proteolytic responses to traffic-related air pollution in lung, liver, and heart of female mice, with an age-dependent loss of adaptive homeostasis.

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Silencing of Inducible Immunoproteasome Subunit Expression by Chemically Modified siRNA and shRNA

Cited by 3 publications

References 41 publications

Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF‑7 cells inï¿½vitro and inï¿½vivo and its mechanism of action

Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF‑7 cells inï¿½vitro and inï¿½vivo and its mechanism of action

Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer

Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles (‘vehicular smog’)

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