miR-15a induces cell apoptosis by targeting BCL2L2 and BCL2 in HPV-positive hypopharyngeal squamous cell carcinoma

Lu, Wuhao; Lin, Feng; Zhang, Yan; Ma, Yunyun; Li, Ping; Wang, Yuanyuan; Du, Yuwen; Chen, Xiaonan; Wu, Shuisheng; Lou, Weihua

doi:10.3892/or.2016.5049

Cited by 21 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Detection of HPC at an earlier stage would be beneficial to patients. Many molecules, such as p16, bcl-2, microRNAs, and cyclin-D1, have been evaluated as candidate biomarkers for HPC [ 4 , 5 ], but none has been widely used in practice because of each belongs to signaling pathways of multiple known or unknown proteins [ 6 ]. Therefore, more effective biomarkers for early diagnosis of HPC are necessary.…”

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma

Tang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Hypopharyngeal cancer (HPC) frequently presents at an advanced stage, resulting in poor prognosis. Although combined surgical therapy and chemoradiotherapy have improved the survival for patients with HPC over the past 3 decades, the mortality rate in late-stage diagnosis of HPC is unsatisfactory. In this study, we performed whole-exome sequencing (WES) of 23 hypopharyngeal tumor and paired adjacent normal tissue to identify novel candidate driver genes associated with hypopharyngeal carcinoma. We identified several copy number variants (CNVs) and 15 somatic mutation genes that were associated with hypopharyngeal carcinoma. Mutations in nine new genes (PRB4, NSD1, REC8, ZNF772, ZNF69, EI24, CYFIP2, NEFH, KRTAP4-5) were also indentified. PRB4 and NSD1 expression were significantly upregulated in hypopharyngeal carcinoma, which was confirmed in an independent cohort using IHC. There was a positive relationship between PRB4 and NSD1. Downregulation of PRB4 by siRNA could inhibit cell growth, colony formation and cell invasion. Notably, we here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. In summary, we pinpoint the predominant mutations in hypopharyngeal carcinoma by WES, highlighting the substantial genetic alterations contributing to hypopharyngeal carcinoma tumorigenesis. We also indentify a novel epigenetically regulatory between PRB4 and NSD1 that contribute to hypopharyngeal carcinoma tumorigenesis. They may become potential prognostic biomarkers and therapeutic target for hypopharyngeal carcinoma treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma

Tang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Wang found miR‐203 could inhibit tumour growth and metastasis through PDPN . MiR‐15a was up‐regulated in HPV‐positive HSCC and might induce tumour apoptosis via BCL2L2 and BCL2 …”

Section: Discussionmentioning

confidence: 99%

“…23 MiR-15a was up-regulated in HPV-positive HSCC and might induce tumour apoptosis via BCL2L2 and BCL2. 24,25 However, many miRNAs are oncogenic by targeting tumour suppressor genes. miR-21 was widely accepted as 'oncomiR', which was overexpressed in various types of cancers including lymphoma, oesophageal cancer, LSCC, HSCC and SCC of oral cavity.…”

Section: Discussionmentioning

confidence: 99%

A 3‐miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post‐operative radiotherapy

Gross

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post‐operative radiotherapy, we used miRNA microarray and qRT‐PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan‐Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR‐200a‐3p, miR‐30b‐5p, miR‐3161, miR‐3605‐5p, miR‐378b and miR‐4451 were up‐regulated, while miR‐200c‐3p, miR‐429 and miR‐4701 were down‐regulated after validation. Moreover, the patients with high expression of miR‐200a‐3p, miR‐30b‐5p and miR‐4451 had significantly worse overall survival (OS) and disease‐specific survival (DSS) than did those with low expression (log‐rank P < .05). Patients with a high‐risk score had significant worse OS and DSS than those with low‐risk score. Finally, after adjusting for other important prognostic confounders, patients with high expression of miR‐200a‐3p, miR‐30b‐5p and miR‐4451 had significantly high risk of overall death and death owing to HSCC and patients with a high‐risk score has approximately 2‐fold increased risk in overall death and death owing to HSCC compared with those with a low‐risk score. These findings indicated that the 3‐miRNA‐based signature may be a novel independent prognostic biomarker for patients given surgery and post‐operative radiotherapy, supporting that these miRNAs may jointly predict survival of HSCC.

show abstract

“…Expression of miRNAs is altered in a number of human diseases from psychiatric disorders (44) to cancer (45). Extensive research shows that miRs play an important role in cell apoptosis (46), suppression of tumor growth, invasion and metastasis in HPV-positive cancer (47). Because of being an upstream regulatory molecule with multiple targets, the changes in levels of miR expression are anticipated to be the cause of multiple dynamic alterations seen in mRNA and protein profiles during carcinogenesis.…”

Section: Micrornas In Carcinogenesismentioning

confidence: 99%

miRNA as viral transcription tuners in HPV-mediated cervical carcinogenesis

et al. 2018

View full text Add to dashboard Cite

High-risk human papillomaviruses (HPVs) are oncogenic DNA viruses that promote carcinogenic signaling by their oncoproteins mainly E6 and E7. A well-defined promoter regulates expression and enhancer region on HPV genome containing number of elements that essentially require a set of cognate host transcription factors to regulate viral promoter gene activity. Expression of these host factors is tightly regulated at multiple levels such as transcriptional, post-transcriptional and post-translational level. Discovery of microRNAs (miRs) in recent years and differential expression of a set of specific miRs in HPV infection and cervical lesions indicate that among various regulatory mechanisms, role of these differentially expressed miRs in the post-transcriptional control is pivotal. Present review analyses and attempts to compile currently available miR data related to HPV infection and cervical carcinogenesis with a special focus on miRs that may regulate expression of the host and viral factors particularly responsible for viral transcription leading to carcinogenic progression of the lesion. Further, the review attempts to assess the therapeutic potential of miR-based strategies in therapeutic targeting of HPV infection during cervical carcinogenesis.

show abstract

miR-15a induces cell apoptosis by targeting BCL2L2 and BCL2 in HPV-positive hypopharyngeal squamous cell carcinoma

Cited by 21 publications

References 26 publications

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma

A 3‐miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post‐operative radiotherapy

miRNA as viral transcription tuners in HPV-mediated cervical carcinogenesis

Contact Info

Product

Resources

About