CDK5 activates Hippo signaling to confer resistance to radiotherapy via upregulating TAZ in lung cancer

Tumor resistance to radiotherapy is a therapeutic challenge in the treatment of patients with lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion; drug resistance; and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.SiRNAs and ShRNAs were used to knock down CDK5 in A549 and H1299 cells. The effects of CDK5 depletion on the tumorigenic behaviors of non-small cell lung cancer (NSCLC) cells were evaluated in vitro and in vivo. Gene expression was examined by RNA-seq and quantitative real-time PCR. Human lung cancer cell line ( A549) were purchased from the American Type Culture Collection (ATCC) and cultured in RPMI-1640 supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin and incubated at 37°C with 5% CO2. Cells transfected with Scramble or CDK5-targeting siRNAs were harvested after 48 h. TRIzol reagent (Takara) was used to extract total RNA. RNA sequencing was conducted with an BGIseq500 platform (BGI-Shenzhen, China). Genes were considered to be significantly differentially expressed by the transcript fragments per kilobase million (FPKM) values if they satisfied the cutoff threshold criteria of a fold change of > 2.0 and a false discovery rate of < 5%.