Genetic variants associated with expression of <i>TCF19</i> contribute to the risk of head and neck cancer in Chinese population

Ji, Pei; Chang, Jiang; Wei, Xiaoyü; Song, Xueyao; Yuan, Hua; Gong, Linnan; Li, Yuancheng; Ding, Dong-sheng; Zhang, Erbao; Yan, Caiwang; Zhu, Meng; Miao, Xiaoping; Wu, Chen; Jin, Guangfu; Hu, Zhibin; Shen, Hongbing; Ma, Hongxia

doi:10.1136/jmedgenet-2020-107410

Cited by 9 publications

(8 citation statements)

References 48 publications

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“…Although GWAS and some candidate gene studies have indicated many risk SNPs are associated with susceptibility to HNSCC, 12,48–50 uncovering disease‐causing variants in noncoding regions and the underlying molecular mechanism in HNSCC remain an open question. In this study, through a two‐stage paired case–control study, we found that rs16854802 A > G and rs3113503 G > C were associated with the risk of HNSCC ( p < 0.01).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the results of public data analysis showed that the elevated LINC01614 expression levels differed significantly between clinical stages and tumor grades, and the level is significantly higher in patients with advanced stage or higher grade of HNSCC (Figure 3C). Although GWAS and some candidate gene studies have indicated many risk SNPs are associated with susceptibility to HNSCC, 12,[48][49][50] uncovering disease-causing variants in noncoding regions and the underlying molecular mechanism in HNSCC remain an open question. In this study, through a two-stage paired case-control study, we found that rs16854802 A > G and rs3113503 G > C were associated with the risk of HNSCC (p < 0.01).…”

Section: Linc01614 Is Highly Expressed In Hnscc Tissues and Implies A...mentioning

confidence: 99%

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Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Hou

Zhou

et al. 2022

Molecular Carcinogenesis

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As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA‐associated single‐nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22–1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15–1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA‐616‐3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR‐616‐3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Linc01614 Is Highly Expressed In Hnscc Tissues and Implies A...mentioning

confidence: 99%

Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Hou

Zhou

et al. 2022

Molecular Carcinogenesis

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“…It was associated with the inflammatory responses in the beta cells of the pancreas and the DNA damage response network. e occurrence and progression of pan-cancer were also affected [16][17][18]. It has been reported recently that TCF19 influences the effect of immunotherapy in lung cancer through nanotechnology by regulating the polarity of the tumor-associated macrophages [31].…”

Section: Discussionmentioning

confidence: 99%

“…e processes of carcinogenesis and immune regulation are significantly affected by the physiological effects of TCF19 activation. Since TCF19 is chronically activated, it is highly expressed in various solid tumors [12][13][14][15] and chronic inflammatory tissues [16][17][18]. e presence of highly expressed TCF19 has been found not only in invasive tumor tissues but also in malignant tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

Immunotherapeutic Value of Transcription Factor 19 (TCF19) Associated with Renal Clear Cell Carcinoma: A Comprehensive Analysis of 33 Human Cancer Cases

Cheng

Hou

Wen

et al. 2022

Journal of Oncology

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Background. We aimed to study the relationship between transcription factor 19 (TCF19) and cancer immunotherapy in the 33 types of human cancers. Methods. The Cancer Genome Atlas database was analyzed to obtain the gene expression data and clinical characteristics for the cases of 33 types of cancers. GSE67501, GSE78220, and IMvigor 210 were included in the immunotherapy cohorts. Relevant data were obtained by analyzing the gene expression database. The prognostic value of TCF19 was determined by analyzing various clinical parameters, such as survival duration, age, the stage of the tumor, and sex of the patients. The single-sample gene set enrichment analysis method was used to determine the activity of TCF19 and the method was also used to assess the differences between the TCF19 transcriptome and protein levels. The correlation between TCF19 and various immune processes and elements such as immunosuppressants, stimulants, and major histocompatibility complexes were analyzed to gain insights into the role of TCF19. The coherent paths associated with the process of TCF19 signal transduction and the influence of TCF19 on immunotherapy biomarkers have also been discussed herein. Finally, three independent immunotherapy methods were used to understand the relationship between TCF19 and immunotherapy response. Results. It was observed that TCF19 was not significantly influenced by the age (5/33), sex (3/33), or tumor stage (3/21) of cancer patients. But the results revealed that TCF19 exhibited a potential prognostic value and could predict the survival rate of the patients. In some cases of this study, the activity and expression of TCF19 were taken at the same level (7/33). Conclusion. TCF19 is strongly related to immune cell infiltration, immunomodulators, and immunotherapy markers. Our study demonstrated that high expression levels of TCF19 are strongly linked with the immune-related pathways. Nevertheless, it is noteworthy that TCF19 is not significantly associated with immunotherapy response.

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“…TCF19 , also known as SC1, was a critical regulator of the key gluconeogenic genes and played an important role in cell proliferation and survival [ 67 , 68 ]. TCF19 promoted the proliferation of various cancer cells, such as lung cancer [ 69 ] and head and neck cancer [ 70 ]. Currently, a study showed that TCF19 might be linked with the proliferation of breast cancer cells [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes in Breast Cancer Induced by Estrogen Plus Progestogens Using Bioinformatic Analysis

Deng

Huang

Shi

et al. 2022

IJMS

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Menopausal hormone therapy (MHT) was widely used to treat menopause-related symptoms in menopausal women. However, MHT therapies were controversial with the increased risk of breast cancer because of different estrogen and progestogen combinations, and the molecular basis behind this phenomenon is currently not understood. To address this issue, we identified differentially expressed genes (DEGs) between the estrogen plus progestogens treatment (EPT) and estrogen treatment (ET) using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data. As a result, a total of 96 upregulated DEGs were first identified. Seven DEGs related to the cell cycle (CCNE2, CDCA5, RAD51, TCF19, KNTC1, MCM10, and NEIL3) were validated by RT-qPCR. Specifically, these seven DEGs were increased in EPT compared to ET (p < 0.05) and had higher expression levels in breast cancer than adjacent normal tissues (p < 0.05). Next, we found that estrogen receptor (ER)-positive breast cancer patients with a higher CNNE2 expression have a shorter overall survival time (p < 0.05), while this effect was not observed in the other six DEGs (p > 0.05). Interestingly, the molecular docking results showed that CCNE2 might bind to 17β-estradiol (−6.791 kcal/mol), progesterone (−6.847 kcal/mol), and medroxyprogesterone acetate (−6.314 kcal/mol) with a relatively strong binding affinity, respectively. Importantly, CNNE2 protein level could be upregulated with EPT and attenuated by estrogen receptor antagonist, acolbifene and had interactions with cancer driver genes (AKT1 and KRAS) and high mutation frequency gene (TP53 and PTEN) in breast cancer patients. In conclusion, the current study showed that CCNE2, CDCA5, RAD51, TCF19, KNTC1, MCM10, and NEIL3 might contribute to EPT-related tumorigenesis in breast cancer, with CCNE2 might be a sensitive risk indicator of breast cancer risk in women using MHT.

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Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population

Cited by 9 publications

References 48 publications

Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Risk SNP‐mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway

Immunotherapeutic Value of Transcription Factor 19 (TCF19) Associated with Renal Clear Cell Carcinoma: A Comprehensive Analysis of 33 Human Cancer Cases

Identification of Candidate Genes in Breast Cancer Induced by Estrogen Plus Progestogens Using Bioinformatic Analysis

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