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FNDC3B 3'UTR shortening escapes from miRNA-mediated gene repression and promotes NPC progression.

FNDC3B 3 'utr 缩短从 miRNA 介导的基因抑制中逸出,促进 NPC 进展。

  • 影响因子:4.60
  • DOI:10.1111/cas.14394
  • 作者列表:"Li YQ","Chen Y","Xu YF","He QM","Yang XJ","Li YQ","Hong XH","Huang SY","Tang LL","Liu N
  • 发表时间:2020-03-30
Abstract

:Alternative polyadenylation (APA), which induces shortening of the 3'UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA-induced 3'UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3'UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3'UTR could escape from miRNA-mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3'UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β-catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knock-down in NPC. Altogether, our results suggested that the 3'UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B-MYH9 -Wnt/β-catenin axis could represent potential targets for individualized treatment in NPC.

摘要

: 替代多聚腺苷酸化 (APA),诱导 3 'utr 缩短,正在成为癌症发生和发展的一个重要特征。然而,APA 诱导的 3 'utr 缩短在鼻咽癌 (NPC) 中的作用和机制仍不清楚。根据我们之前的测序研究,含纤连蛋白 III 型结构域 3B (FNDC3B) 倾向于使用近端多聚腺苷酸化位点,产生更短的 3 'utr。在此,我们发现 3 'utr 较短的 FNDC3B 可以逃避 miRNA 介导的基因抑制,并导致其在 NPC 中的表达增加。敲低 FNDC3B 在体内外抑制 NPC 细胞增殖、迁移、侵袭和转移。FNDC3B 的过表达,特别是那些 3 'utr 较短的,促进了 NPC 进展。此外,机制研究揭示 FNDC3B 可以结合并稳定肌球蛋白重链 9 (MYH9),激活 Wnt/β-catenin 信号通路。此外,MYH9 可逆转 FNDC3B 基因敲除对鼻咽癌的抑制作用。总之,我们的结果表明,FNDC3B mRNA 的 3 'utr 缩短介导了其在 NPC 中的过表达,并通过靶向 myh9 促进 NPC 进展。这一新发现的 FNDC3B-MYH9 -Wnt/β-catenin 轴可能是鼻咽癌个体化治疗的潜在靶点。

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影响因子:2.65
发表时间:2020-01-29
来源期刊:BMJ open
DOI:10.1136/bmjopen-2019-031602
作者列表:["Wendland EM","Kops NL","Comerlato J","Horvath JDC","Bessel M","Sperb D","Pimenta C","de Souza FMA","Mendes Pereira GF","Falcetta FS"]

METHODS:INTRODUCTION:Human papillomavirus (HPV) is the most common sexually transmitted infection and is associated with several types of cancer. The number of cases of HPV-associated head and neck squamous cell carcinomas (HNSCCs), especially oropharyngeal carcinomas, has increased significantly in recent years despite decreased tobacco smoking rates. Currently, no data concerning the risk factors and prevalence of HPV in HNSCC patients in all regions of Brazil are available, making it difficult to promote advances in this field of public health. Therefore, our goal is to determine the impact of infection by HPV, including HPVs with different genotypes, on head and neck cancer and the risk factors associated with the development of head and neck cancer in all regions of Brazil. METHODS AND ANALYSIS:This is a case-control study that will include 622 patients and 622 controls from all regions of Brazil. A questionnaire will be applied to gather information on sociodemographic, behavioural and health factors. Oral, cervical or penile/scrotal, and anal specimens and serum samples will be collected from all participants. Formalin-fixed paraffin-embedded tissue from tumour biopsies will be analysed only in the case group. Molecular and serological analyses will be performed to evaluate the presence and role of HPV in the development of head and neck cancer. ETHICS AND DISSEMINATION:This project was approved by the research ethical committee of the proposing institution (Hospital Moinhos de Vento, number 2.852.060). Ethical approval from the collaborators is currently under evaluation and is not yet complete. The results of this study will be presented at meetings with the Brazilian Ministry of Health through technical reports and to the scientific community at national and international events, with subsequent publication of scientific articles.

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影响因子:2.60
发表时间:2020-01-21
来源期刊:Head & neck
DOI:10.1002/hed.26063
作者列表:["Soldera EB","Ortigara GB","Bonzanini LIL","Schulz RE","Danesi CC","Antoniazzi RP","Linhares Ferrazzo K"]

METHODS:BACKGROUND:Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health-related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis. METHODS:This cross-sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP-14) and the data were analyzed using robust variance poisson regression models. RESULTS:The mean total OHIP-14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP-14 total scores (CI:1.11-2.18) and patients with advanced stage tumors had 31% higher mean OHIP-14 total scores (CI:1.03-1.66) in multivariate analyses. CONCLUSION:OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.

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影响因子:1.62
发表时间:2020-01-22
DOI:10.4317/medoral.23335
作者列表:["Ramos-Vega V","Venegas Rojas B","Donoso Torres W"]

METHODS:BACKGROUND:To immunohistochemically evaluate the association between the presence of cancer-associated fibroblasts (CAFs) and the tumour expression of podoplanin (PDPN) in head and neck squamous cell carcinoma (HNSCC) and their association with clinicopathological variables. MATERIAL AND METHODS:A tissue microarray (TMA) with biopsy sections from patients diagnosed with HNSCC was stained with antibodies against the CAFs marker, α-smooth muscle actin (α-SMA), and PDPN. We subsequently evaluated their expression to determine the association between them and with clinicopathological variables including age, primary tumour site, TNM stage, and tumour differentiation grade. RESULTS:Positive reaction to α-SMA was observed in the tumour stroma, revealing spindle-shaped cells compatible with CAFs, which showed a high expression in 62% of cases and a significant association with laryngeal carcinomas, advanced clinical stages, and lower tumour differentiation (P ≤ 0.05). PDPN staining on tumour cells showed low expression in 72% of cases, and it was not associated with any clinicopathological variable or with the presence of CAFs. CONCLUSIONS:The presence of CAFs in the tumour stroma is related to an aggressive phenotype and could increase as the disease progresses, although based on our findings, it would have no relationship, at least directly, with the expression of PDPN.

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