Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells

Zhao, Li; Zhu, Wenzhuo; Xiong, Liwen; Yu, Xiuchong; Chen, Xi; Lin, Qiang

doi:10.18632/oncotarget.11351

Cited by 40 publications

(50 citation statements)

References 26 publications

(34 reference statements)

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“…STK1, a cell cycle-dependent marker, has prognostic value and is a monitoring factor for NSCLC (29). STK11 is a tumor suppressor gene in lung cancer (30,31), and STK39 acts as a tumor oncogene in NSCLC, promoting cell growth, migration and invasion (32). The results of the present study demonstrated high expression of STK31 and β-catenin in lung cancer tissues and cell lines, suggesting that STK31 may function as an oncogene in lung cancer and may contribute to the carcinogenesis of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

STK31 regulates the proliferation and cell cycle of lung cancer cells via the Wnt/β‑catenin pathway and feedback regulation by c‑myc

Xiong¹,

Xing²,

Zheng³

et al. 2019

Oncol Rep

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Lung cancer, which is a leading cause of cancer-related deaths, is diagnosed at a male to female ratio of 2.1:1. Serine-threonine kinase 31 (STK31) is a novel cancer/testis (CT)-related gene that is highly expressed in several types of cancers, such as lung and colorectal cancer, and plays crucial roles in cancer. In the present study, increased expression of STK31 and β-catenin was observed in lung cancer tissues and cell lines. Downregulation of STK31 expression in lung cancer cells significantly inhibited their proliferation by arresting the cell cycle in the G1 phase concurrent with decreased β-catenin, c-myc and cyclin D1 protein levels, while upregulation of STK31 had the opposite effects. In addition, STK31-induced lung cancer cell viability, proliferation, cell cycle progression, and expression of related genes were completely attenuated by a Wnt/β-catenin inhibitor (XAV939). Similar to XAV939, a c-myc inhibitor (10058-F4) also significantly attenuated STK31-induced proliferation and cell cycle progression in lung cancer cells. Inhibiting c-myc and TRRAP significantly decreased the expression of STK31, and a chromatin immunoprecipitation (ChIP) assay confirmed that c-myc directly bound to the STK31 promoter. These results indicated that STK31 may act as an oncogene in lung cancer and that c-myc may be the transcription factor that promotes STK31 expression. Moreover, the results suggested that c-myc can also regulate STK31 expression in a positive feedback loop, and the downregulation of STK31 in lung cancer cells had an inhibitory effect on cell viability, cell proliferation and cell cycle progression, likely by inactivating the Wnt/β-catenin pathway and positive feedback regulation by c-myc.

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Section: Discussionmentioning

confidence: 99%

STK31 regulates the proliferation and cell cycle of lung cancer cells via the Wnt/β‑catenin pathway and feedback regulation by c‑myc

Xiong¹,

Xing²,

Zheng³

et al. 2019

Oncol Rep

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“…STK39 and OSR1 , which are enriched in the cilia, together with their own activating kinases WNK1 and WNK4 are involved in anion-based signal amplification 37. The high expression of STK39 had inverse effects on cell behaviors in non-small-cell-type lung cancer 38. Zhu et al reported that the WNK1/OSR1/NKCC1 signaling pathway plays an important role in glioma migration 39.…”

Section: Discussionmentioning

confidence: 99%

Analysis of potential genes associated with primary cilia in bladder cancer

Du¹,

Lü²,

Sheng³

et al. 2018

CMAR

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BackgroundDysfunction of primary cilia (PC), which could influence cell cycle and modulate cilia-related signaling transduction, has been reported in several cancers. However, there is no evidence of their function in bladder cancer (BLCA). This study was performed to investigate the presence of PC in BLCA and to explore the potential molecular mechanisms underlying the PC in BLCA.Patients and methodsThe presence of PC was assessed in BLCA and adjacent non-cancerous tissues. The gene expression dataset GSE52519 was employed to obtain differentially expressed genes (DEGs) associated with PC. The mRNA expression of the DEGs were confirmed by Gene Expression Profiling Interactive Analysis. The DEGs properties and pathways were analyzed by Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Genomatix software was used to predict putative transcription factor binding sites (TFBS) in the promoter region of DEGs, and the transcription factors were achieved according to the shared TFBS, which were supported by the ChIP-Sequence data.ResultsPC were found to be reduced in BLCA tissue samples in this study. Seven DEGs were observed to be associated with PC, and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these DEGs exhibited the properties and functions of PC, and that the Hedgehog signaling pathway probably participated in the pathogenesis and progression of BLCA. The mRNA expression of the seven DEGs in 404 BLCA and 28 normal tissue samples were analyzed, and five DEGs including CENPF, STIL, AURKA, STK39 and OSR1 were identified. Five TFBS including CREB, E2FF, EBOX, ETSF and HOXF in the promoter region of five DEGs were calculated and the transcription factors were obtained according to the shared TFBS.ConclusionPC were found to be reduced in BLCA, and the potential molecular mechanisms of PC in BLCA helped to provide novel diagnosis and therapeutic targets for BLCA.

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“…In the present study, we analyzed RNA sequencing data on 10 pairs of NSCLC and non-cancerous lung tissues 12 and detected a significant upregulation of FKBP3 in NSCLC tissues. Previously, FKBP3 was reported to be associated with the activity of HDAC1/2 6 , which can regulate the expression of cell cycle-related genes, such as p21 (CDKN1A) and p27 (CDKN1B), by modulating histone acetylation 13 , 14 .…”

Section: Introductionmentioning

confidence: 98%

FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27

et al. 2017

Self Cite

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FKBP3 is a member of FK506-binding proteins (FKBPs). Little is known about the expression and functional role(s) of FKBP3 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated up-regulation of FKBP3 expression, both at mRNA and protein levels, in NSCLC samples which closely correlated with poor survival in NSCLC patients. In vitro and in vivo experiments revealed that FKBP3 could promote NSCLC cell proliferation. Furthermore, knockdown of FKBP3 significantly decreased histone deacetylase 2 (HDAC2) expression and increased p27 (a cell cycle inhibitor) expression. HDAC2 modulated the acetylation of histone H3K4 by directly binding to the p27 promoter. The proliferation-promoting effect of FKBP3 was dependent on HDAC2 and inhibited by p27. Also, FKBP3 induced HDAC2 promoter activity via inhibiting the ubiquitination of transcription factor Sp1. Additionally, we identified miR-145-5p as a regulator of FKBP3. miR-145-5p overexpression suppressed cell proliferation of NSCLC cells which was abrogated by FKBP3 overexpression. Taken together, our data clearly show that FKBP3/Sp1/HDAC2/p27 control cell proliferation during NSCLC development.

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Role of high expression levels of STK39 in the growth, migration and invasion of non-small cell type lung cancer cells

Cited by 40 publications

References 26 publications

STK31 regulates the proliferation and cell cycle of lung cancer cells via the Wnt/β‑catenin pathway and feedback regulation by c‑myc

STK31 regulates the proliferation and cell cycle of lung cancer cells via the Wnt/β‑catenin pathway and feedback regulation by c‑myc

Analysis of potential genes associated with primary cilia in bladder cancer

FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27

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