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MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

Publication ,  Journal Article
Hu, J; Sun, T; Wang, H; Chen, Z; Wang, S; Yuan, L; Liu, T; Li, H-R; Wang, P; Feng, Y; Wang, Q; McLendon, RE; Friedman, AH; Keir, ST ...
Published in: Cancer Cell
January 11, 2016

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.

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Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

January 11, 2016

Volume

29

Issue

1

Start / End Page

49 / 60

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Oxidoreductases, N-Demethylating
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • MicroRNAs
  • Mice, Nude
  • Humans
  • Glioma
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor
 

Citation

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Hu, J., Sun, T., Wang, H., Chen, Z., Wang, S., Yuan, L., … Wang, X.-F. (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), 49–60. https://doi.org/10.1016/j.ccell.2015.12.005
Hu, Jing, Tao Sun, Hui Wang, Zhengxin Chen, Shuai Wang, Lifeng Yuan, Tingyu Liu, et al. “MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.Cancer Cell 29, no. 1 (January 11, 2016): 49–60. https://doi.org/10.1016/j.ccell.2015.12.005.
Hu, Jing, et al. “MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.Cancer Cell, vol. 29, no. 1, Jan. 2016, pp. 49–60. Pubmed, doi:10.1016/j.ccell.2015.12.005.
Hu J, Sun T, Wang H, Chen Z, Wang S, Yuan L, Liu T, Li H-R, Wang P, Feng Y, Wang Q, McLendon RE, Friedman AH, Keir ST, Bigner DD, Rathmell J, Fu X-D, Li Q-J, Wang X-F. MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B. Cancer Cell. 2016 Jan 11;29(1):49–60.
Journal cover image

Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

January 11, 2016

Volume

29

Issue

1

Start / End Page

49 / 60

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Oxidoreductases, N-Demethylating
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • MicroRNAs
  • Mice, Nude
  • Humans
  • Glioma
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor