Targeting Rab26 to Conquer Cisplatin-Resistant Lung Cancer with Self-Assembled DNA Nanomaterials

Abstract

Overcoming cisplatin-based drug resistance in lung cancer remains an enormous challenge in clinical tumor therapy worldwide. Recent studies have reported that some Rab GTPases are involved in multiple aspects of tumor progression, including invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. In particular, Rab26 is essential to vital processes such as vesicle-mediated secretion, cell growth, apoptosis, and autophagy. In this study, we developed a nanosystem based on programmed DNA self-assembly of Rab26 siRNA-loaded nanoparticles (siRNP). We demonstrated that siRNP could be effectively transfected into cisplatin-resistant A549 (A549/DDP) cells. These siRab26-carrying nanoparticles induced apoptosis and inhibited the disruption of autophagy. The combination therapy of siRab26 knockdown with cisplatin could improve the antitumor therapy compared with a single one in vitro. In nude mice, siRNP enhanced the chemosensitivity of cisplatin-resistant cells and inhibited tumor xenograft development. These outcomes suggest that siRNP is an effective platform for lung cancer therapy in cases exhibiting drug resistance.

RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance

“…RAB GTPases could also serve as biomarkers for resistance to certain small molecule chemotherapeutic drugs ( Wei et al, 2022 ; Li C. et al, 2023 ). For example, RAB1b is reported to be involved in sorafenib-resistance of HCC ( Xu et al, 2023 ), and high expression of RAB26 promotes the cisplatin-based drug resistance in lung cancer ( Wang et al, 2023 ). Here, we analyze the role of RAB42 in drug resistance in pan-cancer.…”