p38γ overexpression promotes osteosarcoma cell progression

Shi, Ce; Cheng, Weyland; Yin, Wei; Li, Dazhuang; Zhou, Lei; Zhu, Yu‐Cheng; Zhou, Xiaozhong

doi:10.18632/aging.103708

Cited by 6 publications

(12 citation statements)

References 33 publications

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“…The two non-overlapping shRNAs targeting p38γ (p38γ-shRNA-s1 and p38γ-shRNA-s2, from Dr. Shi [ 22 ]) and a negative control with the scrambled non-sense sequence (shC) were constructed into GV248 lentiviral vectors provided by Shanghai Genechem Co. (Shanghai, China). The full-length p38γ cDNA sequence (also from Dr. Shi [ 22 ]) was sub-cloned into the GV248 lentiviral vector (Genechem Co.). The lentivirus was produced by transfecting HEK293T cells with the plasmids using a lentivirus packaging mix (Genechem Co.).…”

Section: Methodsmentioning

confidence: 99%

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma

et al. 2022

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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.

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Section: Methodsmentioning

confidence: 99%

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma

et al. 2022

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“…p38γ can also play a cancer-promoting part in OS by stimulating Rb phosphorylation and cyclin E1/A expression and regulating G1-S phase transition [36]. Accordingly, present study shows that mRNA and protein expression of p38γ in human OS tissue and primary OS cells were significantly higher than that in human primary osteoblasts and OB-6 osteoblastic cells [36].…”

Section: Cutaneous T-cell Lymphomamentioning

confidence: 53%

“…Using CRISPR-Cas9 inhibits oncogenes such as p38γ gene in some tumors, which may become a promising anti-cancer strategy. Researchers have used CRISPR-Cas9-induced p38γ knockout to inhibit the in vitro progression of human OS cells and the growth, proliferation and migration of human CRC cells and human RCC cells and induce significant apoptosis [34][35][36]. On the other hand, it is reported that CRISPR-Cas9 can be used as a powerful tool to manipulate epigene regulation to treat cancer and reshape abnormal epigenetic patterns and can selectively and genetically alter gene expression [73].…”

Section: Discussionmentioning

confidence: 99%

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The Role of p38γ in Cancer: From review to outlook

Xu¹,

Li²,

Dai³

et al. 2021

Int. J. Biol. Sci.

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p38γ is a member of the p38 Mitogen Activated Protein Kinases (p38 MAPKs). It contains four subtypes in mammalian cells encoded by different genes including p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). Recent studies revealed that p38γ may exhibit a crucial role in tumorigenesis and cancer aggressiveness. Despite the large number of published literatures, further researches are demanded to clarify its role in cancer development, the tissue-specific function and associated novel treatment strategies. In this article, we provide the latest view on the connection between p38γ and malignant tumors, highlighting the function of p38γ. The clinical value of p38γ is also discussed, helping the translation into the remarkable therapeutic strategy in tumor diseases.

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“…The p38 MAPKs also had high sequence homology with CDK family members, thus could cooperate with CDKs, and regulate the cell cycle. For liver tumorigenesis, the p38 MAPKs were essential for the cancer cell cycle progression and are identified as the promising therapeutic targets for the disease (40). BDNF participates in the activation of MAPKs and is a novel functional protein in HCC (41).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

et al. 2021

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Hepatocellular carcinoma is a malignancy with a low survival rate globally, and there is imperative to unearth novel natural phytochemicals as effective therapeutic strategies. Licochalcone A is a chalcone from Glycyrrhiza that displayed various pharmacological efficacy. A globally transcriptome analysis was carried out to reveal the gene expression profiling to explore Licochalcone A's function as an anti-cancer phytochemical on HepG2 cells and investigate its potential mechanisms. Altogether, 6,061 dysregulated genes were detected (3,414 up-regulated and 2,647 down-regulated). SP1 was expected as the transcription factor that regulates the functions of most screened genes. GO and KEGG analysis was conducted, and the MAPK signaling pathway and the FoxO signaling pathway were two critical signal pathways. Protein-protein interaction (PPI) network analysis based on STRING platform to discover the hub genes (MAPK1, ATF4, BDNF, CASP3, etc.) in the MAPK signaling pathway and (AKT3, GADD45A, IL6, CDK2, CDKN1A, etc.) the FoxO signaling pathway. The protein level of essential genes that participated in significant pathways was consistent with the transcriptome data. This study will provide an inclusive understanding of the potential anti-cancer mechanism of Licochalcone A on hepatocellular, signifying Licochalcone A as a promising candidate for cancer therapy.

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p38γ overexpression promotes osteosarcoma cell progression

Cited by 6 publications

References 33 publications

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma

The Role of p38γ in Cancer: From review to outlook

Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

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