Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression

Wang, Yu; Ledet, Russell J.; Imberg-Kazdan, Keren; Logan, Susan K.; Garabedian, Michael J.

doi:10.18632/oncotarget.10284

Cited by 21 publications

(17 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the description in the STRING or GeneCards database, DNAH8 is a force-generating protein of the respiratory cilia and is also involved in sperm motility. In addition, DNAH8 is highly expressed in prostate cancer [21]. Titin appears to be a key component of the vertebrate striated muscles [22].…”

Section: Functional Enrichment Of the Unique Hbmec-ev Proteinsmentioning

confidence: 99%

HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles

András

Sewell

Toborek

2020

IJMS

View full text Add to dashboard Cite

Amyloid beta (Aβ) depositions are more abundant in HIV-infected brains. The blood-brain barrier, with its backbone created by endothelial cells, is assumed to be a core player in Aβ homeostasis and may contribute to Aβ accumulation in the brain. Exposure to HIV increases shedding of extracellular vesicles (EVs) from human brain endothelial cells and alters EV-Aβ levels. EVs carrying various cargo molecules, including a complex set of proteins, can profoundly affect the biology of surrounding neurovascular unit cells. In the current study, we sought to examine how exposure to HIV, alone or together with Aβ, affects the surface and total proteomic landscape of brain endothelial EVs. By using this unbiased approach, we gained an unprecedented, high-resolution insight into these changes. Our data suggest that HIV and Aβ profoundly remodel the proteome of brain endothelial EVs, altering the pathway networks and functional interactions among proteins. These events may contribute to the EV-mediated amyloid pathology in the HIV-infected brain and may be relevant to HIV-1-associated neurocognitive disorders.

show abstract

Section: Functional Enrichment Of the Unique Hbmec-ev Proteinsmentioning

confidence: 99%

HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles

András

Sewell

Toborek

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Another speculation, to hypothesize a novel therapeutic strategy in positive ERG prostate cancer patients, was based on the analysis of the co-expressed protein-coding genes and lncRNAs. The upregulation of the Wnt pathway and its inhibition emerged as a promising strategy against prostate cancer [ 46 ], although thinking about the most appropriate approach is imperative for the pervasive role of the Wnt pathway in normal tissue homeostasis. Several approaches have been taken into account for inhibiting the Wnt pathway, such as LGK974, a drug that targets the Wnt-specific acyltransferase porcupine, and the tankyrase inhibitor XAV939 [ 46 ], and the growing interest in the inhibition of the Wnt pathway in prostate cancer models confirms the validity of the therapeutic hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach

Summa

Palazzo

Caputo

et al. 2021

IJMS

View full text Add to dashboard Cite

Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and long non-coding(lnc)-SAYSD1-1, able to discriminate ERG/not-ERG subtypes, were demonstrated to be positive prognostic biomarkers in ERG-positive patients. Furthermore, we performed a comparison between mutated prostate cancer, identified as “classified”, and a group of patients with no peculiar genomic alteration, named “not-classified”. Moreover, LINC00920 lncRNA overexpression has been linked to a better outcome of the hormone regimen. Through the feature selection approach, it was found that the overexpression of lnc-ZMAT3-3 is related to low-grade patients, and three lncRNAs: lnc-SNX10-87, lnc-AP1S2-2, and ADPGK-AS1 showed, through a co-expression analysis, significant correlation values with potentially druggable pathways. In conclusion, the data mining of publicly available data and robust bioinformatic analyses are able to explore the unknown biology of malignancies.

show abstract

“…An integrated analysis of RNA-Seq data and qRT-PCR results revealed that DNAH5 may play an important role in the development of colorectal cancer, and it might be useful for diagnosis, prognosis prediction and therapy [33]. DNAH8 has been reported to be a novel regulator of the androgen receptor that is associated with metastatic tumors and poor prognosis in patients with prostate cancer [34]. In invasive micropapillary carcinomas of the breast, DNAH9 has a substantially elevated mutation rate [35].…”

Section: Discussionmentioning

confidence: 99%

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients

Zhu

Yang

et al. 2019

J Transl Med

View full text Add to dashboard Cite

Background The dynein axonemal heavy chain (DNAH) family of genes encode the dynein axonemal heavy chain, which is involved in cell motility. Genomic variations of DNAH family members have been frequently reported in diverse kinds of malignant tumors. In this study, we analyzed the genomic database to evaluate the mutation status of DNAH genes in gastric adenocarcinoma and further identified the significance of mutant DNAH genes as effective molecular biomarkers for predicting chemotherapy response in gastric cancer patients. Methods We analyzed the clinical and genomic data of gastric cancer patients published in The Cancer Genome Atlas (TCGA) project. Data on chemotherapy response, overall survival (OS) and chemotherapy-free survival were retrieved. Then, we verified the results via targeted sequencing of gastric cancer patients with similar clinical characteristics but different chemotherapeutic outcomes. Results In total, 132 gastric adenocarcinoma patients undergoing chemotherapy treatment from TCGA were included in our study. Somatic mutations in all 13 members of the DNAH family of genes were associated with different chemotherapy responses. Compared with patients with wild-type DNAH genes (n = 59), a significantly higher proportion of those with mutations in DNAH genes (n = 73) (55.9% vs 80.8%) responded to chemotherapy (P = 0.002). Moreover, DNAH mutations were correlated with significantly better OS (P = 0.027), chemotherapy-free survival (P = 0.027), fluoropyrimidine-free survival (P = 0.048) and platinum-free survival (P = 0.014). DNAH mutation status was an independent risk factor for OS (P = 0.015), chemotherapy-free survival (P = 0.015) and platinum-free survival (P = 0.011). We identified somatic mutations in 27 (42.2%) of the 64 stage III gastric adenocarcinoma patients receiving fluoropyrimidine-based chemotherapy by targeted exon sequencing with strict screening conditions. In our own cohort, a significantly higher proportion of patients (n = 32) with DNAH mutations than patients with wild-type DNAH genes (n = 32) had a good prognosis (OS > 48 months) (70.4% vs 35.1%) (P = 0.005). Conclusions Dynein axonemal heavy chain gene mutations contribute positively to chemotherapy sensitivity in gastric cancer patients. Electronic supplementary material The online version of this article (10.1186/s12967-019-1867-6) contains supplementary material, which is available to authorized users.

show abstract

Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression

Cited by 21 publications

References 41 publications

HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles

HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles

Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients

Contact Info

Product

Resources

About