The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1

Iwona Hirschler-Laszkiewicz, Fernanda Festa, Suming Huang, George Lucian Moldovan, Claudia Nicolae, Ashna Dhoonmoon, Lei Bao, Kerry Keefer, Shu jen Chen, Hong Gang Wang, Joseph Y. Cheung, Barbara A. Miller

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Transient receptor potential channel melastatin 2 (TRPM2) is highly expressed in cancer and has an essential function in preserving viability through maintenance of mitochondrial function and antioxidant response. Here, the role of TRPM2 in cell survival was examined in neuroblastoma cells with TRPM2 deletion with CRISPR technology. Viability was significantly decreased in TRPM2 knockout after doxorubicin treatment. RNA sequence analysis and RT-qPCR revealed reduced RNAs encoding master transcription regulators FOXM1 and E2F1/2 and downstream cell cycle targets including Cyclin B1, CDK1, PLK1, and CKS1. CHIP analysis demonstrated decreased FOXM1 binding to their promoters. Western blotting confirmed decreased expression, and increased expression of CDK inhibitor p21, a CKS1 target. In cells with TRPM2 deletion, cell cycle progression to S and G2/M phases was reduced after treatment with doxorubicin. RNA sequencing also identified decreased DNA repair proteins in cells with TRPM2 deletion after doxorubicin treatment, and DNA damage was increased. Wild type TRPM2, but not Ca2+-impermeable mutant E960D, restored live cell number and reconstituted expression of E2F1, FOXM1, and cell cycle/DNA repair proteins. FOXM1 expression alone restored viability. TRPM2 is a potential therapeutic target to reduce tumor proliferation and increase doxorubicin sensitivity through modulation of FOXM1, E2F1, and cell cycle/DNA repair proteins.

Original languageEnglish (US)
Article number6311
JournalScientific reports
Issue number1
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General


Dive into the research topics of 'The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1'. Together they form a unique fingerprint.

Cite this