Advances in Targeting Cancer-Associated Genes by Designed siRNA in Prostate Cancer

Bahreyni, Amirhossein; Luo, Honglin

doi:10.3390/cancers12123619

Cited by 5 publications

(2 citation statements)

References 99 publications

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“…Previously, many people believed that it was essentially impossible to change gene expression in the tumor cells in patients. However, recent research indicates that siRNAloaded nanoparticles targeted several gene expressions of tumor cells in patients (14). Even though many siRNA-targeted genes are known for cellular growth and survival, targeting genes associated with T-cell interaction could be vital.…”

Section: Discussionmentioning

confidence: 99%

Application of gene therapy for reversing T-cell dysfunction in cancer

Hyun Lee,

Rin Lee

2022

J Emerg Invest

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T cells are the key players of antitumor function that sense antigens produced by tumor cells and specifically target cancer cells to induce cell death. Therefore, it is widely understood that T cells are critical for cancer immunotherapy. Many recent studies discovered that T cells enter a dysfunctional or inactivated state. Cancer cells induce functional impairment of T cells by sustained expression of inhibitory receptors in T cells. Therefore, reversing T-cell dysfunction is critical for increasing the efficacy of tumor immunotherapy. In this research, we analyzed the cellular inhibition and activation of T cells using two cell line models: Jurkat (T cells) and MDA-MB-231 (breast cancer cells). We hypothesized that the knockdown of T-cell inhibition-causing genes might reverse the T-cell dysfunction caused by cancer cells. Therefore, we targeted Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1) gene in T cells and programmed death-ligand 1 (CD274) in cancer cells. We used small interference RNA (siRNA) to knock down the target gene. We used four μg/ml of lipopolysaccharide (LPS) to activate Jurkat cells. MDA-MB-231 co-culture with Jurkat cells reduced IL-2 expression level on Jurkat cells. We found that siRNA targeting CD274 in MDA-MB-231 reversed the reduced IL-2 expression level on Jurkat induced by Jurkat and MDA-MB-231 co-culture. Also, when the PCSK1 knockdown Jurkat cells and CD274 knockdown MDA-MB-231 were co-cultured, the most effective recovery of IL-2 expression level in Jurkat cells was observed. Overall, this study provides a novel strategy for reactivating T cells whose activation has been suppressed from cancer cells.

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Section: Discussionmentioning

confidence: 99%

Application of gene therapy for reversing T-cell dysfunction in cancer

Hyun Lee,

Rin Lee

2022

J Emerg Invest

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“…After the discovery of RNA interference (RNAi) in 1990s, this therapeutic tool obtained much attention in pre‐clinical and clinical settings (Ashrafizadeh, Hushmandi, et al, 2020; Ashrafizadeh, Zarrabi, et al, 2020; FiBahreyni & Luo, 2020; Fire et al, 1998; Lee, Kim, et al, 2016; Mirzaei, Gholami, et al, 2021; Mirzaei, Gholami, et al, 2021; Mirzaei, Mahabady, et al, 2021). Small interfering RNA (siRNA) is double‐stranded RNA with 21‐25 nucleotides capable of silencing target genes (Kleinman, Kaneko, et al, 2012; Zamore, Tuschl, et al, 2000).…”

Section: Noncoding Rnasmentioning

confidence: 99%