Regulation of miR106b cluster through the RB pathway

Mechanismand functional targets

Chellappagounder Thangavel, Ettickan Boopathi, Adam Ertel, Meng Lim, Sankar Addya, Paolo Fortina, Agnieszka K. Witkiewicz, Erik S. Knudsen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The RB pathway plays a critical role in proliferation control that is commonly subverted in tumor development. However, restoration of RB pathway function can be elicited in many tumor cells by the inhibition of CDK4/6 activity that leads to dephosphorylation of RB and subsequent repression of E2F-mediated transcription. In this context, active RB/E2F complexes inhibit the expression of a critical program of coding genes that promote cell cycle progression. However, the non-coding RNA target genes downstream from RB that could be relevant for tumor biology remain obscure. Here, miRNA gene expression profiling identified the miR106b cluster as being efficiently repressed with CDK4/6 inhibition in an E2F and RB-dependent manner. Importantly, the miR106B-cluster is intragenic of MCM7, and through a series of functional studies, the basis of MCM7 regulation and concordant expression of the miRNA species within the 106b cluster was determined. Importantly, RB-mediated repression of the 106b cluster enhances the transcript levels of p21Cip1 and PTEN. These data provide a mechanistic basis for cross-talk between the RB pathway and p21 and PTEN through the regulation of the MCM7/miR106b locus.

Original languageEnglish (US)
Pages (from-to)98-111
Number of pages14
JournalCell Cycle
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

MicroRNAs
cdc Genes
Neoplasms
Untranslated RNA
Gene Expression Profiling
Genes

Keywords

  • CDK4/6 inhibitor
  • MCM7
  • Mir106b-cluster
  • P21
  • PD 0332991
  • PTEN
  • Retinoblastoma protein (pRB)
  • Transcriptional repression

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Thangavel, C., Boopathi, E., Ertel, A., Lim, M., Addya, S., Fortina, P., ... Knudsen, E. S. (2013). Regulation of miR106b cluster through the RB pathway: Mechanismand functional targets. Cell Cycle, 12(1), 98-111. https://doi.org/10.4161/cc.23029

Regulation of miR106b cluster through the RB pathway : Mechanismand functional targets. / Thangavel, Chellappagounder; Boopathi, Ettickan; Ertel, Adam; Lim, Meng; Addya, Sankar; Fortina, Paolo; Witkiewicz, Agnieszka K.; Knudsen, Erik S.

In: Cell Cycle, Vol. 12, No. 1, 01.01.2013, p. 98-111.

Research output: Contribution to journalArticle

Thangavel, C, Boopathi, E, Ertel, A, Lim, M, Addya, S, Fortina, P, Witkiewicz, AK & Knudsen, ES 2013, 'Regulation of miR106b cluster through the RB pathway: Mechanismand functional targets', Cell Cycle, vol. 12, no. 1, pp. 98-111. https://doi.org/10.4161/cc.23029
Thangavel C, Boopathi E, Ertel A, Lim M, Addya S, Fortina P et al. Regulation of miR106b cluster through the RB pathway: Mechanismand functional targets. Cell Cycle. 2013 Jan 1;12(1):98-111. https://doi.org/10.4161/cc.23029
Thangavel, Chellappagounder ; Boopathi, Ettickan ; Ertel, Adam ; Lim, Meng ; Addya, Sankar ; Fortina, Paolo ; Witkiewicz, Agnieszka K. ; Knudsen, Erik S. / Regulation of miR106b cluster through the RB pathway : Mechanismand functional targets. In: Cell Cycle. 2013 ; Vol. 12, No. 1. pp. 98-111.
@article{96105aaed1754b449ac21f3e02e8cccb,
title = "Regulation of miR106b cluster through the RB pathway: Mechanismand functional targets",
abstract = "The RB pathway plays a critical role in proliferation control that is commonly subverted in tumor development. However, restoration of RB pathway function can be elicited in many tumor cells by the inhibition of CDK4/6 activity that leads to dephosphorylation of RB and subsequent repression of E2F-mediated transcription. In this context, active RB/E2F complexes inhibit the expression of a critical program of coding genes that promote cell cycle progression. However, the non-coding RNA target genes downstream from RB that could be relevant for tumor biology remain obscure. Here, miRNA gene expression profiling identified the miR106b cluster as being efficiently repressed with CDK4/6 inhibition in an E2F and RB-dependent manner. Importantly, the miR106B-cluster is intragenic of MCM7, and through a series of functional studies, the basis of MCM7 regulation and concordant expression of the miRNA species within the 106b cluster was determined. Importantly, RB-mediated repression of the 106b cluster enhances the transcript levels of p21Cip1 and PTEN. These data provide a mechanistic basis for cross-talk between the RB pathway and p21 and PTEN through the regulation of the MCM7/miR106b locus.",
keywords = "CDK4/6 inhibitor, MCM7, Mir106b-cluster, P21, PD 0332991, PTEN, Retinoblastoma protein (pRB), Transcriptional repression",
author = "Chellappagounder Thangavel and Ettickan Boopathi and Adam Ertel and Meng Lim and Sankar Addya and Paolo Fortina and Witkiewicz, {Agnieszka K.} and Knudsen, {Erik S.}",
year = "2013",
month = "1",
day = "1",
doi = "10.4161/cc.23029",
language = "English (US)",
volume = "12",
pages = "98--111",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - Regulation of miR106b cluster through the RB pathway

T2 - Mechanismand functional targets

AU - Thangavel, Chellappagounder

AU - Boopathi, Ettickan

AU - Ertel, Adam

AU - Lim, Meng

AU - Addya, Sankar

AU - Fortina, Paolo

AU - Witkiewicz, Agnieszka K.

AU - Knudsen, Erik S.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - The RB pathway plays a critical role in proliferation control that is commonly subverted in tumor development. However, restoration of RB pathway function can be elicited in many tumor cells by the inhibition of CDK4/6 activity that leads to dephosphorylation of RB and subsequent repression of E2F-mediated transcription. In this context, active RB/E2F complexes inhibit the expression of a critical program of coding genes that promote cell cycle progression. However, the non-coding RNA target genes downstream from RB that could be relevant for tumor biology remain obscure. Here, miRNA gene expression profiling identified the miR106b cluster as being efficiently repressed with CDK4/6 inhibition in an E2F and RB-dependent manner. Importantly, the miR106B-cluster is intragenic of MCM7, and through a series of functional studies, the basis of MCM7 regulation and concordant expression of the miRNA species within the 106b cluster was determined. Importantly, RB-mediated repression of the 106b cluster enhances the transcript levels of p21Cip1 and PTEN. These data provide a mechanistic basis for cross-talk between the RB pathway and p21 and PTEN through the regulation of the MCM7/miR106b locus.

AB - The RB pathway plays a critical role in proliferation control that is commonly subverted in tumor development. However, restoration of RB pathway function can be elicited in many tumor cells by the inhibition of CDK4/6 activity that leads to dephosphorylation of RB and subsequent repression of E2F-mediated transcription. In this context, active RB/E2F complexes inhibit the expression of a critical program of coding genes that promote cell cycle progression. However, the non-coding RNA target genes downstream from RB that could be relevant for tumor biology remain obscure. Here, miRNA gene expression profiling identified the miR106b cluster as being efficiently repressed with CDK4/6 inhibition in an E2F and RB-dependent manner. Importantly, the miR106B-cluster is intragenic of MCM7, and through a series of functional studies, the basis of MCM7 regulation and concordant expression of the miRNA species within the 106b cluster was determined. Importantly, RB-mediated repression of the 106b cluster enhances the transcript levels of p21Cip1 and PTEN. These data provide a mechanistic basis for cross-talk between the RB pathway and p21 and PTEN through the regulation of the MCM7/miR106b locus.

KW - CDK4/6 inhibitor

KW - MCM7

KW - Mir106b-cluster

KW - P21

KW - PD 0332991

KW - PTEN

KW - Retinoblastoma protein (pRB)

KW - Transcriptional repression

UR - http://www.scopus.com/inward/record.url?scp=84872321372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872321372&partnerID=8YFLogxK

U2 - 10.4161/cc.23029

DO - 10.4161/cc.23029

M3 - Article

VL - 12

SP - 98

EP - 111

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 1

ER -