Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation

Abstract

Significant advancements have been achieved in the area of molecular targeted therapy for lung adenocarcinoma (LUAD). However, the complex molecular patterns and high heterogeneity of LUAD confine the efficacy of these therapies to a specific subset of patients; therefore, it is necessary to explore novel targets for LUAD treatment. The expression levels of anillin (ANLN) in LUAD were analyzed using the Gene Expression Profiling Interactive Analysis database. Furthermore, the association between ANLN gene expression and patient survival outcomes was evaluated using the Kaplan-Meier Plotter. Subsequently, small interfering RNA (siRNA) transfection was performed to knock down ANLN in A549 and H1299 cell lines, after which, TUNEL, colony formation and Transwell assays were conducted to assess cell death, colony formation and migration, respectively. Additionally, western blot analysis was performed to analyze the expression levels of caspase-1, interleukin (IL)-18 (IL-18), IL-1β, NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC) and cleaved gasdermin D (GSDMD) following ANLN knockdown. The results revealed that ANLN mRNA expression was significantly increased in LUAD tissues compared with adjacent normal samples. Furthermore, the expression levels of ANLN displayed an increasing trend with advancing clinical stage. Furthermore, patients with high ANLN expression levels exhibited poor overall survival rates compared with those with low ANLN expression levels. Subsequent ANLN knockdown experiments indicated elevated cell death rate, and reduced colony formation and migration in both A549 and H1299 cells. Additionally, ANLN knockdown resulted in increased protein expression levels of pyroptosis-associated molecules, including caspase-1, NLRP3, cleaved-GSDMD, IL-1β, ASC and IL-18 in both A549 and H1299 cells. In conclusion, ANLN represents an important gene and a promising therapeutic target for LUAD. Its potential as a therapeutic target makes it an interesting candidate for further exploration in the development of novel treatment strategies for LUAD.

Differential whole-genome doubling based signatures for improvement on clinical outcomes and drug response in patients with breast cancer

“…This is in concordance with a positive correlation between the expression of KIF18A and ANLN. Furthermore, numerous studies have reported the overexpression of ANLN as a potential biomarker of lung cancer progression [ 67 , 68 ]. The elevated expression of CCNE2 is also significantly correlated with advanced tumors and worse OS in lung cancer [ 69 , 70 ].…”

ANLN Promotes the Proliferation and Migration of Gallbladder Cancer Cells via STRA6-Mediated Activation of PI3K/AKT Signaling

“…Recent studies have revealed the involvement of ANLN in the initiation and progression of various cancer types. For example, in lung cancer, the knockdown of ANLN can activate pyroptosis and inhibit the progression of lung adenocarcinoma [32]. Similarly, elevated ANLN expression in liver tumors is linked to poor prognosis, and ANLN knockdown has been demonstrated to inhibit the occurrence and progression of liver tumors by influencing cytokinesis impairment.…”