Predictive Role and HuR Mechanisms of Regulation in the Brain Tumours (HUR)

The HuR protein binds to AU-rich elements in the untranslated 3' region of messenger RNA, thus allowing their stabilization. Its targets include multiple cell cycle regulating proteins, cytokines and growth factors. In some cancers, its overall expression level but especially its cytoplasmic expression are correlated to a higher grade and constitute a poor prognostic factor. To date, HuR's deregulation mechanisms remain poorly understood. A few experimental studies have shown the role of certain microARNS, or of post-translational modifications. In brain tumours, HuR expression, its prognostic value and its deregulation mechanisms have been little studied to date.

The first part of the project will be a monocentric retrospective study of human brain tumour samples collected during biopsies or surgical removal. We will first evaluate HuR expression in 140 brain tumors, including 40 meningiomas and 100 gliomas of increasing grade, and look for a correlation with histological grade and survival. We will then apprehend the consequences of its deregulation by analyzing different factors involved in the cell cycle and stress response markers. Finally, we will study the mechanisms of HuR deregulation by analyzing the expression level of several microRNAs (miR16, miR519) and the methylation state of HuR.

The second part of the project will focus on cell lines from human brain tumours. We will first attempt to confirm the interactions between HuR and markers involved in the cell cycle and stress response, then the regulation of HuR by its methylation and by microRNAs (miR16 and miR519). We would also like to study the consequences of HuR inhibition and overexpression on cell proliferation, under various conditions of induced stress (pharmacological agents, physical stress). Finally, we will study the consequences of an experimental vitamin B12 deficiency on HuR expression and tumor cell adaptation to stress.

Study Overview

• Status: Unknown
• Conditions: Brain Tumours

• Study Type: Observational
• Enrollment (Anticipated): 140

Contacts and Locations

Study Locations

• France
  • Vandoeuvre Les Nancy, France, 54511
    • Recruiting
    • Guillaume GAUCHOTTE
    • Contact: Guillaume GAUCHOTTE, PU-PH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patient with braim tumor (meningioma, glioma, glioblastoma)

Description

Inclusion Criteria

• Grade I and II meningiomas (WHO)
• Diffuse grade II glioma (astrocytoma, oligodendroglioma)
• Grade III anaplastic gliomas (astrocytomas and anaplastic oligodendrogliomas)
• Grade IV glioblastoma

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
level HuR's immunohistochemical expression	at diagnosis
time progression-free	through study completion, an average 3 years
time overall survival	through study completion, an average 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
methyl-HuR level		1 day at diagnosis
PHH3 level		1 day at diagnosis
MCM6 level		1 day at diagnosis
Ki-67 level		1 day at diagnosis
cyclin D1 level		1 day at diagnosis
Bcl-2		1 day at diagnosis
pPERK level		1 day at diagnosis
ATF6 level		1 day at diagnosis
SIRT1 level		1 day at diagnosis
IRE-1α level		1 day at diagnosis
HIF-1α level		1 day at diagnosis
caspase 3 activated level		1 day at diagnosis
VEGF level		1 day at diagnosis
CARM1 level	Vitamin B12 metabolism	1 day at diagnosis
miR16 expression level by qRT-PCR		1 day at diagnosis
miR519 expression level by qRT-PCR		1 day at diagnosis

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 2011/APJC/HUR/GAUCHOTTE/MS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No