Integrative analysis of miRNAs-mRNAs reveals that miR-182 up-regulation contributes to proliferation and invasion of nasopharyngeal carcinoma by targeting PTEN.
MiRNAs-mRNAs 的整合分析表明，miR-182 上调通过靶向 PTEN 促进鼻咽癌的增殖和侵袭。
- 作者列表："Shi Z","Wang R","Huang L","Chen X","Xu M","Zha D","Ma Y
OBJECTIVE:Several miRNAs have been found to be abnormally expressed during nasopharyngeal carcinoma development. Nevertheless, the interaction between miRNAs and downstream genes remains unexploited. In this study, we aim to investigate miRNAs-mRNAs interaction and the mechanism of miR-182 in NPC. RESULTS:Integrative analysis identified several hub-miRNAs that drive NPC pathogenesis. The expression of miR-182 was notably increased in 32 NPC tissues and cell lines (CNE1 and 5-8F). Up-regulation of miR-182 was strongly correlated with poor prognosis of NPC patients. Moreover, the proliferation and invasion of NPC cells were notably increased in miR-182 mimics condition and decreased in miR-182 inhibitor condition. Furthermore, PTEN was verified to be a target of miR-182 and overexpression of PTEN could abrogate the promotion effect of miR-182 mimics on NPC invasion. CONCLUSIONS:We identified several hub-miRNAs that may drive NPC pathogenesis. MiR-182 could promote proliferation and invasion of NPC cells via targeting PTEN, which provides a new insight into the clinical therapy of NPC. MATERIALS AND METHODS:Genome-wide miRNAs of NPC tissues was analyzed using high-throughput sequencing and bioinformatics tools. QRT-PCR experiment was conducted to measure relative expression level. Dual-luciferase reporter assay was used to verify target relationship. The proliferation and invasion of transfected cells were measured by CCK-8 and transwell assay.
目的: 研究发现几种 miRNAs 在鼻咽癌发生发展过程中表达异常。尽管如此，miRNAs 和下游基因之间的相互作用仍未被利用。在这项研究中，我们旨在探讨 miRNAs-mRNAs 相互作用和 miR-182 在 NPC 中的机制。 结果: 整合分析确定了几个驱动 NPC 发病机制的 hub-miRNAs。在 32 例鼻咽癌组织和细胞系 (CNE1 和 5-8F) 中，miR-182 的表达明显增加。MiR-182 的上调与鼻咽癌患者的不良预后密切相关。此外，在模拟 miR-182 条件下，鼻咽癌细胞的增殖和侵袭能力明显增强，而在 miR-182 抑制剂条件下，增殖和侵袭能力明显降低。此外，PTEN 被证实是 miR-182 的靶点，过表达 PTEN 可消除 miR-182 模拟物对鼻咽癌侵袭的促进作用。 结论: 我们鉴定了几种可能驱动 NPC 发病机制的 hub-miRNAs。MiR-182 通过靶向 PTEN 促进鼻咽癌细胞的增殖和侵袭，为鼻咽癌的临床治疗提供了新的思路。 材料和方法: 使用高通量测序和生物信息学工具分析 NPC 组织的全基因组 miRNAs。QRT-PCR 实验测定相对表达水平。采用双荧光素酶报告基因检测方法验证靶标关系。CCK-8 和 transwell 法检测转染细胞的增殖和侵袭能力。
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.
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.
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.