AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

Ni, Li; Xue, Wei; Yuan, Huairui; Dong, Baijun; Ding, Yong; Liu, Yongfeng; Jiang, Min; Kan, Shan; Sun, Tongyu; Ren, Jiale; Pan, Qiang; Li, Xiang; Zhang, Peiyuan; Hu, Guohong; Wang, Yan; Wang, Xiaoming; Li, Qintong; Qin, Jun

doi:10.1172/jci91144

Cited by 97 publications

(118 citation statements)

References 57 publications

(70 reference statements)

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“…c ). These candidates are key proteins in the cancer‐related pathways/processes mTOR2/AKT, TGFbeta and alternative splicing, respectively, and their expression has been shown to mediate poor outcome and resistance to therapy in different cancer types including thyroid cancer …”

Section: Resultsmentioning

confidence: 99%

“…3c). These candidates are key proteins in the cancer-related pathways/processes mTOR2/AKT, TGFbeta and alternative splicing, respectively, and their expression has been shown to mediate poor outcome 24,25 and resistance to therapy 26 in different cancer types including thyroid cancer. [27][28][29] We used TargetScan version 7.0 30 to search for hsa-miR-139-5p-matched sites within the 3'UTR sequence of the candidate genes and found one 7 mer-seed matched-site for each of them (Supporting Information Fig.…”

Section: Hsa-mir-139-5p Regulates the Expression Of Proteins Related mentioning

confidence: 99%

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Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

Montero‐Conde

Graña‐Castro

Martín-Serrano

et al. 2019

Intl Journal of Cancer

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It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow‐up of 96 months. MiRNome profiles correlated with tumor‐specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa‐miR‐139‐5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease‐free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa‐miR‐139‐5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa‐miR‐139‐5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa‐miR‐139‐5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa‐miR‐139‐5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

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Section: Resultsmentioning

confidence: 99%

Section: Hsa-mir-139-5p Regulates the Expression Of Proteins Related mentioning

confidence: 99%

Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

Montero‐Conde

Graña‐Castro

Martín-Serrano

et al. 2019

Intl Journal of Cancer

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“…Analysis in human tumor data sets was carried out essentially as previously described (62). The SETD2 gene signature was derived from our own gene expression profile data set.…”

Section: Methodsmentioning

confidence: 99%

“…The SCs and progenitor signatures were derived from GEO GSE6894 (64), which contained 367 significantly highly expressed genes in colon crypt compared with colon top. In order to define the degree of gene signature manifestation within profiles from external human colon tumor data sets (e.g., GEO GSE35982), we used the previously described t score metric (62,67), which was defined for each external profile as the 2-sided t statistic comparing the average of the SETD2-induced genes with the average of the SETD2-repressed genes (genes within the human tumor data set were first centered to SD from the median of the primary tumor specimens). For a given data set, the t score contrasted the patterns of the SETD2-induced genes with those of the SETD2-repressed genes to derive a single value denoting coordinate expression of the 2 gene sets.…”

Section: Methodsmentioning

confidence: 99%

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Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Yuan¹,

Ni²,

Fu³

et al. 2017

Journal of Clinical Investigation

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135

127

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Multilevel Regulation of NF‐κB Signaling by NSD2 Suppresses Kras‐Driven Pancreatic Tumorigenesis

Feng,

Niu,

et al. 2024

Advanced Science

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Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer with a dismal overall prognosis. NSD2 is an H3K36‐specific di‐methyltransferase that has been reported to play a crucial role in promoting tumorigenesis. Here, the study demonstrates that NSD2 acts as a putative tumor suppressor in Kras‐driven pancreatic tumorigenesis. NSD2 restrains the mice from inflammation and Kras‐induced ductal metaplasia, while NSD2 loss facilitates pancreatic tumorigenesis. Mechanistically, NSD2‐mediated H3K36me2 promotes the expression of IκBα, which inhibits the phosphorylation of p65 and NF‐κB nuclear translocation. More importantly, NSD2 interacts with the DNA binding domain of p65, attenuating NF‐κB transcriptional activity. Furthermore, inhibition of NF‐κB signaling relieves the symptoms of Nsd2‐deficient mice and sensitizes Nsd2‐null PDAC to gemcitabine. Clinically, NSD2 expression decreased in PDAC patients and negatively correlated to nuclear p65 expression. Together, the study reveals the important tumor suppressor role of NSD2 and multiple mechanisms by which NSD2 suppresses both p65 phosphorylation and downstream transcriptional activity during pancreatic tumorigenesis. This study opens therapeutic opportunities for PDAC patients with NSD2 low/loss by combined treatment with gemcitabine and NF‐κBi.

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AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis

Cited by 97 publications

References 57 publications

Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

Hsa‐miR‐139‐5p is a prognostic thyroid cancer marker involved in HNRNPF‐mediated alternative splicing

Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis

Multilevel Regulation of NF‐κB Signaling by NSD2 Suppresses Kras‐Driven Pancreatic Tumorigenesis

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