MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
Abstract
The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating
cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here,
we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic
microenvironment via suppressing the expression of an epigenetic regulator KDM1B and
modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and
several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors
(HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely
with KDM1B while correlating positively with HIF1α and GBM progression in patients.
These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently
activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.
Type
Journal articleSubject
AnimalsBrain Neoplasms
Cell Hypoxia
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Glioma
Humans
Mice, Nude
MicroRNAs
Neoplasm Recurrence, Local
Oxidoreductases, N-Demethylating
Tumor Microenvironment
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https://hdl.handle.net/10161/11667Published Version (Please cite this version)
10.1016/j.ccell.2015.12.005Publication Info
(2016). MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating
Cell Adaptation to Hypoxia by Targeting KDM1B. Cancer Cell, 29(1). pp. 49-60. 10.1016/j.ccell.2015.12.005. Retrieved from https://hdl.handle.net/10161/11667.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Darell Doty Bigner
E. L. and Lucille F. Jones Cancer Distinguished Research Professor, in the School
of Medicine
The Causes, Mechanisms of Transformation and Altered Growth Control and New Therapy
for Primary and Metastatic Tumors of the Central Nervous System (CNS). There are
over 16,000 deaths in the United States each year from primary brain tumors such as
malignant gliomas and medulloblastomas, and metastatic tumors to the CNS and its covering
from systemic tumors such as carcinoma of the lung, breast, colon, and melanoma. An
estimated 80,000 cases of primary brain tumors were expected to
Allan Howard Friedman
Guy L. Odom Distinguished Professor of Neurosurgery, in the School of Medicine
At the present time, I am participating in collaborative research in the areas of
primary malignant brain tumors, epilepsy and subarachnoid hemorrhage. Primary malignant
brain tumors are increasing in frequency. Patients harboring glioblastoma, the most
malignant primary brain tumor, have a life expectancy of less than one year. In collaboration
with the Division of Neurology and the Department of Pathology, clinical and laboratory
trials have been initiated to identify better treat
Stephen Thomas Keir
Professor in Neurosurgery
Brain Tumors, Preclinical Testing, Translational Research
Qi-Jing Li
Adjunct Associate Professor in the Department of Immunology
Recent clinical success in cancer immunotherapy, including immune checkpoint blockades
and chimeric antigen receptor T cells, have settled a long-debated question in the
field: whether tumors can be recognized and eliminated by our own immune system, specifically,
the T lymphocyte. Meanwhile, current limitations of these advanced treatments pinpoint
fundamental knowledge deficits in basic T cell biology, especially in the context
of tumor-carrying patients. Aiming to develop new immunotherapi
Roger Edwin McLendon
Professor of Pathology
Brain tumors are diagnosed in more than 20,000 Americans annually. The most malignant
neoplasm, glioblastoma, is also the most common. Similarly, brain tumors constitute
the most common solid neoplasm in children and include astrocytomas of the cerebellum,
brain stem and cerebrum as well as medulloblastomas of the cerebellum. My colleagues
and I have endeavored to translate the bench discoveries of genetic mutations and
aberrant protein expressions found in brain tumors to better understan
Jeffrey Charles Rathmell
Adjunct Associate Professor in the Department of Pharmacology and Cancer Biology
My laboratory studies the mechanisms and role of glucose metabolism in lymphocyte
survival and activation. We have found that dramatic increases in glucose metabolism
are necessary for lymphocytes to survive and mount immune responses. Excessive glucose
metabolism, however, can lead to T cell hyperactivation and autoimmunity. A key mechanism
for control of lymphocyte glucose metabolism is regulation of glucose uptake by the
glucose transporter, Glut1. Interestingly, upregulation of Glut1 and glu
Xiao-Fan Wang
Donald and Elizabeth Cooke Distinguished Professor of Cancer Research, in the School
of Medicine
The current research in the Wang laboratory mainly focuses on the elucidation of molecular
nature and signaling mechanisms associated with the initiation of cellular senescence.
In addition, we continue to study changes in tumor microenvironment that promotes
tumor progression and metastasis, particularly how tumor cells interact with the immune
system. Ultimately, we hope that our studies in these areas to lead to the development
of novel therapeutics for the treatment of various types of human
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