TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway

Sun, Tianshui; Bi, Fangfang; Liu, Zhuonan; Yang, Qing

doi:10.1186/s12967-021-02781-x

Cited by 27 publications

(20 citation statements)

References 43 publications

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“…Furthermore, lots of TMEM proteins are known to be involved in cancer-related signaling pathways like EGFR-induced NF-κB activation or TGF-β signaling [ 6 , 7 ]. Several TMEMs meet the criteria of prognostic biomarkers, as their expression has been correlated with metastasis, tumor recurrence, and patient survival [ 5 , 8 , 9 ]. Identifying TMEMs engaged in tumor development and progression is a promising approach to finding the new therapeutic targets for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Koteluk

Bielicka

Lemańska

et al. 2021

Cancers

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Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.

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Section: Introductionmentioning

confidence: 99%

The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Koteluk

Bielicka

Lemańska

et al. 2021

Cancers

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“…3–5 As there are often no obvious symptoms in the early stage of OV, many patients with epithelial OV are in the advanced stage of cancer when they are diagnosed, which also leads to the relatively low five-year survival rate of OV. 6,7 If OV can be detected in the early stage, the survival rate and quality of life of OV patients can be improved, and the cost of treatment and related economic burden can be reduced. 8…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma

Liang

Zhong

et al. 2021

Exp Biol Med (Maywood)

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In this study, we aim to identify the clinical significance of basonuclin 1 ( BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of –2.339 (95% CI: –3.649 to –1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445–0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low- BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 ( FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

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“…LDB2 also works in transcriptional regulation and has been found to have a lower expression in liver cancer as well ( Yu et al 2017 ). PDGRFB was recently associated with TMEM119 , another member of the UCEC triangle GRN, and AKT , a previously identified endometrial cancer hub gene, in ovarian cancer ( Huo et al 2019 ; Sun et al 2021 ).…”

Section: Discussionmentioning

confidence: 98%

Identification of condition-specific biomarker systems in uterine cancer

Hickman

Hang

Pauly

et al. 2021

G3 Genes|Genomes|Genetics

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Uterine cancer is the fourth most common cancer among women, projected to affect 66,000 US women in 2021. Uterine cancer often arises in the inner lining of the uterus, known as the endometrium, but can present as several different types of cancer, including endometrioid cancer, serous adenocarcinoma, and uterine carcinosarcoma. Previous studies have analyzed the genetic changes between normal and cancerous uterine tissue to identify specific genes of interest, including TP53 and PTEN. Here we used Gaussian Mixture Models to build condition-specific gene coexpression networks for endometrial cancer, uterine carcinosarcoma, and normal uterine tissue. We then incorporated uterine regulatory edges and investigated potential coregulation relationships. These networks were further validated using differential expression analysis, functional enrichment, and a statistical analysis comparing the expression of transcription factors and their target genes across cancerous and normal uterine samples. These networks allow for a more comprehensive look into the biological networks and pathways affected in uterine cancer compared with previous singular gene analyses. We hope this study can be incorporated into existing knowledge surrounding the genetics of uterine cancer and soon become clinical biomarkers as a tool for better prognosis and treatment.

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TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway

Cited by 27 publications

References 43 publications

The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma

Identification of condition-specific biomarker systems in uterine cancer

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