MicroRNA regulation of the small Rho GTPase regulators—complexities and opportunities in targeting cancer metastasis

Brock A. Humphries, Zhishan Wang, Chengfeng Yang

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


The small Rho GTPases regulate important cellular processes that affect cancer metastasis, such as cell survival and proliferation, actin dynamics, adhesion, migration, invasion and transcriptional activation. The Rho GTPases function as molecular switches cycling between an active GTP-bound and inactive guanosine diphosphate (GDP)-bound conformation. It is known that Rho GTPase activities are mainly regulated by guanine nucleotide exchange factors (RhoGEFs), GTPase-activating proteins (RhoGAPs), GDP dissociation inhibitors (RhoGDIs) and guanine nucleotide exchange modifiers (GEMs). These Rho GTPase regulators are often dysregulated in cancer; however, the underlying mechanisms are not well understood. MicroRNAs (miRNAs), a large family of small non-coding RNAs that negatively regulate protein-coding gene expression, have been shown to play important roles in cancer metastasis. Recent studies showed that miRNAs are capable of directly targeting RhoGAPs, RhoGEFs, and RhoGDIs, and regulate the activities of Rho GTPases. This not only provides new evidence for the critical role of miRNA dysregulation in cancer metastasis, it also reveals novel mechanisms for Rho GTPase regulation. This review summarizes recent exciting findings showing that miRNAs play important roles in regulating Rho GTPase regulators (RhoGEFs, RhoGAPs, RhoGDIs), thus affecting Rho GTPase activities and cancer metastasis. The potential opportunities and challenges for targeting miRNAs and Rho GTPase regulators in treating cancer metastasis are also discussed. A comprehensive list of the currently validated miRNA-targeting of small Rho GTPase regulators is presented as a reference resource.

Original languageEnglish
Article number1092
Issue number5
StatePublished - May 2020

Bibliographical note

Funding Information:
This work was supported by a Research Scholar Grant (RGS-15-026-01-CSM) from the American Cancer Society to C.Y. Brock Humphries, PhD, was supported by an American Cancer Society—Michigan Cancer Research Fund Postdoctoral Fellowship, PF-18-236-01-CCG.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cancer
  • Metastasis
  • MicroRNAs
  • Rho GTPase regulators
  • Rho GTPases
  • RhoGAPs
  • RhoGDIs
  • RhoGEFs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'MicroRNA regulation of the small Rho GTPase regulators—complexities and opportunities in targeting cancer metastasis'. Together they form a unique fingerprint.

Cite this