Faculty

Yin-Yuan Mo, PhD

Professor, Department of Pharmacology and Toxicology
Director, Cancer Genetics Program
Office: G651-3
(601) 815-6849

Research interests

  • MicroRNA-mediated tumorigenesis
  • LncRNAs impact on various aspects of tumorigenesis through regulatin of gene expression
  • Application of CRISPR/Cas9 technology to cancer research
  • Acidosis-mediated cell signaling and tumorigenesis

Research synopsis

My laboratory has been focusing on understanding of epigenetic regulation of genes involved in tumorigenesis and chemoresistance in four primary areas:

  • MicroRNA-meditated tumorigenesis. It is well known now that the human genome is actively transcribed. However, protein-coding genes account for only 2% and the rest are non-coding RNAs, including microRNAs and long non-coding RNAs. Our early work has focused on microRNAs and tried to understand how microRNAs impact different aspects of tumorigenesis. For example, we have demonstrated that miR-21 functions as an oncogene whereas miR-145 functions as a tumor suppressor. In particular, many of these microRNAs are directly or indirectly involved in the AKT pathway, leading to tumor growth and invasion.
  • LncRNAs impact various aspects of tumorigenesis through regulation of gene expression. Recently, our research has extended to long non-coding RNAs (lncRNAs). We have shown that several lncRNAs are dysregulated in cancer and they impact tumor cell growth, invasion and metastasis because they can regulate gene expression through various mechanisms. For instance, Linc-RoR functions as a p53 repressor in response to DNA damage. Importantly, p53 can induce Linc-RoR and other lncRNAs such Loc285194, providing evidence that these lncRNAs are associated with the p53 pathway, serving as p53 regulators or p53 targets. Our recent study suggests that AK023948 promotes AKT activity through interaction with DHX9 and p85.
  • Application of CRISPR/Cas9 technology to cancer research. We have developed several valuable techniques or reagents that are important to lncRNA research such as dual gRNA approach for knockout of lncRNAs via CRISPR/Cas9 system. We have also generated CRISPR/Cas9-based libraries (knockout and SAM gene activation) against a focus group of lncRNAs. For example, along with an AKT reporter system, we identify AK023948 as a positive regulator of AKT.
  • Acidosis-mediated cell signaling and tumorigenesis. Microenvironment of solid tumors is often acidic. However, it is not clear how tumor cells sense the acidic signal and then activate acidosis-induced signaling. We have recently reported that acidosis leads to activation of AKT and NF-κB, and cell invasion through acid-sensing ion channels (ASICs). Furthermore, acidosis induces MALAT1 which is required for acidosis-induced NF-κB activation. Thus, there is a critical need for better understanding of this acidosis-ASIC-AKT-MALAT1-NF-κB axis in cancer.

Selected publications

  • LncRNA AK023948 is a positive regulator of AKT. Koirala P, Huang J, Ho TT, Wu F, Ding X, Mo YY. Nat Commun. 2017 Feb 8;8:14422. doi: 10.1038/ncomms14422. PubMed PMID: 28176758.
  • Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines. Ho TT, Zhou N, Huang J, Koirala P, Xu M, Fung R, Wu F, Mo YY. Nucleic Acids Res. 2015 Feb 18;43(3):e17.