Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/β-catenin pathway

Lin, Qiao; Qi, Qianle; Hou, Sen; Chen, Zhe; Jiang, Nan; Zhang, Laney; Lin, Chenghe

doi:10.4149/neo_2021_210304n276

Cited by 7 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A positive association between Wnt target biological pathways, and the PS-score was identified previously. Among the pyroptosis-related signature genes, AHNAK2 knockdown was previously reported to inhibit the Wnt pathway ( Lin et al, 2021 ). In addition, AHNAK2 expression was reported to be significantly positively correlated with the PS-score in TCGA and two GEO-BC cohorts ( Figures 8A–C ).…”

Section: Resultsmentioning

confidence: 99%

“…Wnt signaling is an essential biological process, which plays critical roles in tumorigenesis and prognosis ( Reya and Clevers 2005 ). Among the DEGs between distinct pyroptosis-related subtypes, AHNAK2 knockdown was previously reported to activate the Wnt pathway and correlated with tumor immune cell infiltration while its role in BC is rarely reported ( Lin et al, 2021 ; Zheng et al, 2021 ). We found a significant positive association between AHNAK2 expression and the PS-score.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer

Yan

Cao

Wang

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: Bladder cancer (BC) is a leading cause of death from malignancy, with significant heterogeneity in the immunotherapeutic responsiveness of advanced status. Pyroptosis, a newly discovered inflammatory programmed cell death, is confirmed to play an indispensable role in tumorigenesis and anti-tumor activity. However, the effect of pyroptosis on the tumor-immune landscape remodeling and immunotherapy in BC remains elusive.Methods: We comprehensively evaluated the mRNA expression and genomic alterations of 33 pyroptosis-related genes (PRGs) in BC and evaluated the patterns of pyroptosis in publicly available BC datasets. An unsupervised clustering method was used to classify patients into distinct patterns. Then, we established a pyroptosis-related signature score (PS-score) model to quantify the pyroptosis-related patterns of individual BC patients using principal component analysis. Furthermore, we correlated the patterns with the immune landscape and response efficacy of immunotherapy.Results: Two pyroptosis-related patterns were identified in BC, and distinct patterns showed various immune characteristics. Patterns with a high expression level of PRGs exhibited a survival advantage and showed higher infiltration of cytotoxic lymphocytes. Tumors with a low PS-score were characterized by high tumor-infiltrating lymphocytes and considered “hot.” Further analysis revealed that the PS-score was an independent prognostic factor and could predict the response to immunotherapy for patients with advanced BC. We found a significant positive association between AHNAK2, AHNAK nucleoprotein 2, expression, and PS-score. Functional assays showed that AHNAK2 knockdown was correlated with attenuated invasive ability.Conclusion: This work comprehensively demonstrated the potential function of pyroptosis-related patterns in the bladder tumor-immune landscape and identified their therapeutic liability in immunotherapy. Our study enhanced our understanding of the immune landscape and provided a new approach toward more effective immunotherapy strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer

Yan

Cao

Wang

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…proposed that Del-AHNAK2 mut increased the TMB and NAL level, activated cytotoxic T lymphocyte (CTL) effector functions and interferon-gamma (IFN)-γ signaling, and eventually initiated the therapeutic immune response of NSCLC ( 39 ). AHNAK2 knockdown was previously reported to activate the Wnt pathway and correlated with tumor immune cell infiltration thyroid cancer ( 40 ).…”

Section: Discussionmentioning

confidence: 97%

Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart

et al. 2022

View full text Add to dashboard Cite

Penoscrotum extramammary Paget disease (pEMPD) is a rare cutaneous carcinoma with an unknown cell origin. pEMPD always presents as a tumor in situ with an indolent process, whereas some progress into invasive forms with more aggressive behavior. The in situ and invasive cases display different morphologies and biological behavior, and thus far, a relationship between these two components has not been demonstrated. Immunohistochemistry was used to disclose the immunotype of pEMPD, and the results revealed that invasive/in situ pEMPD possessed with some identical immunophenotypes such as CK7, P63, and CK10, which inferred the clonal relatedness. The variable expressions of GCDFP-15 and carcino embryonic antigen hinted that tumor cell origin might be an epidermal sweat gland in epiderma. In our cohort, invasive pEMPD presented increased expression of androgen receptor and decreased MUC5CA expression, and these two changes might bring to the shift of invasive phenotype. To better understanding the relationship between these distinct tumor forms, we performed whole exome sequencing testing to evaluate overlapping genomic alterations of six paired invasive/in situ pEMPDs. The results showed that missense mutation was the predominant mutation type, and C>T transition accounted for 65.1% in all SNP mutation. Among the top 20 differential genes obtained from the six paired invasive/in situ pEMPD analysis, MUC4 (one missense, one in frame del, and one multi-hit), AHNAK2 (two missense and one multi-hit), DOT1L (two missense and one multi-hit), and FRG1 (two missense and one-multi hit) mutations were most enriched in invasive pEMPDs, which postulated that these genes may play roles in the disease progression.

show abstract

“…Lin et al reported that the knockdown of AHNAK2 restrained EMT in thyroid carcinoma in vitro by regressing the Wnt/β-catenin signaling pathway. 11 Liu et al showed that AHNAK2 promotes EMT in lung cancer via the TGF-β/Smad3 pathway. 12 TGF-β1 induces the upregulation of EMT-related genes, promoting tumor cell migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

“…The main underlying mechanism is epithelial–mesenchymal transitions (EMT). Lin et al reported that the knockdown of AHNAK2 restrained EMT in thyroid carcinoma in vitro by regressing the Wnt/ β ‐catenin signaling pathway 11 . Liu et al showed that AHNAK2 promotes EMT in lung cancer via the TGF‐ β /Smad3 pathway 12 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF‐β1/Smad3 signaling pathway

Zhu

Zhang

et al. 2022

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background Idiopathic pulmonary fibrosis (IPF) is a chronic and advanced interstitial lung disease with poor prognosis. AHNAK nucleoprotein 2 (AHNAK2) is a macromolecular protein that is important for cell migration and muscle membrane repair. The protein acts via epithelial–mesenchymal transition (EMT), which is a key mechanism in the pathogenesis of IPF. However, very few studies have elucidated the effect of AHNAK2 in the development of IPF. Therefore, we aimed to determine the role of AHNAK2 in IPF development. Methods C57BL/6 mice were induced with bleomycin, while A549 and Beas‐2b pulmonary epithelial cell lines were treated with TGF‐β1 to induce IPF model. The expression of AHNAK2 was detected using immunohistochemistry staining in vivo, and real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blotting (WB) in vitro. C57BL/6 mice were injected with adeno‐associated virus (AAV)‐sh NC or AAV‐sh AHNAK2 and the pulmonary function and EMT marker expression were measured. The migratory abilities of the two transforming growth factor beta 1 (TGF‐β1)‐induced cell lines were examined using wound‐healing and Transwell assays after transfection with si‐NC, si‐AHNAK2‐1 and ‐2. EMT marker expression was detected using RT‐qPCR and WB. Smad3 and phosphorylated‐Smad3 of the two cells were examined using WB. Following Smad3 inhibition by Smad3 phosphorylation inhibitor (SIS3), TGF‐β1‐induced cell migration and EMT marker expression were evaluated again after different transfections. Results AHNAK2 expression was higher in the IPF model than in the normal model in vivo and in vitro. Partial inhibition of AHNAK2 suppressed the EMT process and improved pulmonary ventilation and compliance in the mouse model of IPF. Similarly, knockdown of AHNAK2 suppressed the migration of pulmonary epithelial cells and reversed EMT. Furthermore, Smad3 of the two TGF‐β1‐induced cell lines was not activated when AHNAK2 was inhibited. When SIS3 inhibited the activation of Smad3, the suppression of AHNAK2 had no effect on A549 and Beas‐2b, regardless of TGF‐β1 induction. Conclusions Inhibition of AHNAK2 alleviates pulmonary fibrosis and partially reverses EMT by inhibiting the TGF‐β1/Smad3 signaling pathway. Therefore, AHNAK2 is a potential therapeutic target for IPF.

show abstract

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/β-catenin pathway

Cited by 7 publications

References 22 publications

Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer

Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer

Cell origin and genome profile difference of penoscrotum invasive extramammary Paget disease compared with its in situ counterpart

Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF‐β1/Smad3 signaling pathway

Contact Info

Product

Resources

About