AHNAK as a Prognosis Factor Suppresses the Tumor Progression in Glioma

Zhao, Zijin; Xiao, Shifu; Yuan, Xianrui; Yuan, Jian; Zhang, Chi; Li, Haoyu; Su, Jun; Wang, Xiangyu; Liu, Qing

doi:10.7150/jca.20277

Cited by 31 publications

(36 citation statements)

References 34 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have suggested possible roles for Ahnak in mediating various signaling events, such as the actin cytoskeleton network, PI3K/AKT and MAPK/ERK signaling pathways, DNA damage signaling, cell contacts, and calcium channel regulation, which are involved in carcinogenesis (37,38). Thus, Ahnak deficiency may promote the neoplastic and malignant transformation of lung epithelial cells by targeting multiple pathways in addition to the Smad pathway.…”

Section: Discussionmentioning

confidence: 99%

AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development

Park

Kim

Choi

et al. 2018

Molecular Cancer Research

View full text Add to dashboard Cite

AHNAK is known to be a tumor suppressor in breast cancer due to its ability to activate the TGFβ signaling pathway. However, the role of AHNAK in lung tumor development and progression remains unknown. Here, the Ahnak gene was disrupted to determine its effect on lung tumorigenesis and the mechanism by which it triggers lung tumor development was investigated. First, AHNAK protein expression was determined to be decreased in human lung adenocarcinomas compared with matched nonneoplastic lung tissues. Then, Ahnak mice were used to investigate the role of AHNAK in pulmonary tumorigenesis. Ahnak mice showed increased lung volume and thicker alveolar walls with type II pneumocyte hyperplasia. Most importantly, approximately 20% of aged Ahnak mice developed lung tumors, and Ahnak mice were more susceptible to urethane-induced pulmonary carcinogenesis than wild-type mice. Mechanistically, Ahnak deficiency promotes the cell growth of lung epithelial cells by suppressing the TGFβ signaling pathway. In addition, increased numbers of M2-like alveolar macrophages (AM) were observed in Ahnak lungs, and the depletion of AMs in Ahnak lungs alleviated lung hyperplastic lesions, suggesting that M2-like AMs promoted the progression of lung hyperplastic lesions in Ahnak-null mice. Collectively, AHNAK suppresses type II pneumocyte proliferation and inhibits tumor-promoting M2 alternative activation of macrophages in mouse lung tissue. These results suggest that AHNAK functions as a novel tumor suppressor in lung cancer. The tumor suppressor function of AHNAK, in murine lungs, occurs by suppressing alveolar epithelial cell proliferation and modulating lung microenvironment. .

show abstract

Section: Discussionmentioning

confidence: 99%

AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development

Park

Kim

Choi

et al. 2018

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…It has been reported that low expression of AHNAK can effectively inhibit breast cancer cell invasion and proliferation as a tumor suppressor . In glioma, AHNAK can depress tumor development and serve as a biomarker of tumor prognosis . Moreover, low expression of AHNAK in melanoma indicates poor prognosis .…”

Section: Introductionmentioning

confidence: 99%

“…20,21 In glioma, AHNAK can depress tumor development and serve as a biomarker of tumor prognosis. 22 Moreover, low expression of AHNAK in melanoma indicates poor prognosis. 23 Nevertheless, the role of AHNAK in the development and prognosis of liver cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV‐related liver diseases

Sun

Liu

et al. 2018

Cancer Medicine

View full text Add to dashboard Cite

The purpose of this study was to investigate the correlation between AHNAK methylation level in peripheral blood mononuclear cells (PBMC) and the progression of hepatitis B virus (HBV)‐related liver disease. Bioinformatics methods were applied to evaluate the AHNAK methylation level in PBMC and T cells at different stages of HBV related liver disease, to investigate the correlation between AHNAK methylation and clinical features, as well as to compare the methylation site of AHNAK in cancer tissues and adjacent tissues. Subsequently, the differentially expressed gene analysis technique was used to analyze the liver disease‐related genes and immune‐related pathways in hepatitis B patients with different pathological changes. Finally, promoter methylation and mRNA expression of AHNAK gene in liver cancer and adjacent tissues were determined by quantitative polymerase chain reaction (Q‐PCR), and the diagnostic value of AHNAK methylation level in hepatopathy was evaluated by receiver operating characteristic (ROC) curve. The promoter methylation level of AHNAK gene in PBMCs decreased with the progression of HBV‐related liver disease, and showed significant difference among the patients with various HBV‐related liver diseases (P = 0.0001). The AHNAK methylation level in PBMCs and T cells was negatively associated with age, white blood cell count, CREA, drinking, and positively associated with APTT and HbsAg. Higher mRNA expression of AHNAK was found in liver cancer tissues than that of adjacent tissues (P < 0.001), and the methylation level in PBMC decreased with the progression of hepatitis B‐related liver disease. The area under the ROC curve (ROC) was 0.883 (P < 0.001) in diagnosis of chronic hepatitis B (CHB), 0.885 (P < 0.001) in diagnosis of compensatory liver cirrhosis, 0.955 (P < 0.001) in diagnosis of decompensated liver cirrhosis, 0.981 (P < 0.001) in diagnosis of hepatocellular carcinoma. Our results revealed that AHNAK methylation level in peripheral blood decreases with the progression of hepatitis B‐related liver disease. This provided a potential differential diagnostic method for HBV‐related hepatopathies, and thus an early detective tool for liver cancer.

show abstract

“…PPARG is considered as a prognostic marker [30,31]. Our results con rmed that AHNAK acted as a potential tumor suppressor and could be a reliable clinical prognostic indicator [32,33]. Nevertheless, the potential role of TRBC1 in cancer development remains unclear.…”

Section: Discussionmentioning

confidence: 55%

Development of an immunogenomics-based prognostic index model of laryngeal squamous cell carcinoma

Shen

Zhou

Dong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The immune system greatly affects the prognosis of various malignancies. Studies on differentially expressed immune-related genes (IRGs) in the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) have rarely been reported.Methods: In this paper, the prognostic potentials of IRGs in LSCC were explored. The RNAseq dataset containing differentially expressed IRGs and corresponding clinical information of LSCC patients was obtained from The Cancer Genome Atlas (TCGA). A total of 371 up-regulated and 61 down-regulated IRGs were identified. Subsequent functional enrichment analysis revealed that the pathway of IRGs was mainly enriched in the cytokine-cytokine receptor interaction. Then, 30 IRGs with prognostic potentials in LSCC were screened out, and the regulatory network induced by relevant transcription factors (TFs) were constructed.Results: Finally, multivariate Cox regression analysis was conducted to assess the prognostic potential of 15 IRGs after adjustment of clinical factors and LSCC patients were classified into 2 subgroups based on different outcomes. The gene expression of the model was verified by other independent databases. Nomogram including the 15 IRGs signature was established and shown some clinical net beneft. Intriguingly, B cells were significantly enriched in the low-risk group. Conclusion:These findings may contribute to the development of potential therapeutic targets and biomarkers for the new-immunotherapy of LSCC.

show abstract

AHNAK as a Prognosis Factor Suppresses the Tumor Progression in Glioma

Cited by 31 publications

References 34 publications

AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development

AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development

Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV‐related liver diseases

Development of an immunogenomics-based prognostic index model of laryngeal squamous cell carcinoma

Contact Info

Product

Resources

About