The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma

Abstract

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

“…Zhu et al found a close association between ALDH1B1 expression and prognosis of locally-advanced NPC ( Zhu et al, 2022 ). In addition, studies have suggested that p38γ is a key oncogene and an important therapeutic target for NPC ( Yin et al, 2022 ), and that Circ_0028007 promotes NPC progression by adsorbing miR-656-3p and increasing ELF2 expression ( Ma and Li, 2022 ). These findings indicate that targeted therapy for NPC is a promising area for further research.…”

The mitochondrial protein YME1 Like 1 is important for non-small cell lung cancer cell growth

“…Quantitative real time-PCR (qPCR), Western blotting and co-immunoprecipitation (Co-IP) was described early as well 30 , 31 . CellROX staining of ROS content, tissue/cellular ATP contents and the mitochondrial complex I activity were measured using the described protocols 29 , 37 . Figure S1 listed the uncropped blotting images.…”

The mitochondrial RNA polymerase POLRMT promotes skin squamous cell carcinoma cell growth

“…Other functional assays , including the caspase-3 activity assay, Western blotting assay, mRNA detection by qRT-PCR were described in early studies [ 22 , 31 ]. Measuring ATP contents was described previously [ 40 ]. The intensity of lipid peroxidation in cell and tissue lysates was examined through a thiobarbituric acid reactive substance (TBAR) kit (Cayman Chemical, MI).…”