IDH1 gene mutation activates Smad signaling molecules to regulate the expression levels of cell cycle and biological rhythm genes in human glioma U87‑MG cells

Abstract

Isocitrate dehydrogenase1 (IDH1) mutation is the most important genetic change in glioma. The most common IDH1 mutation results in the amino acid substitution of argi‑ nine 132 (Arg/R132), which is located at the active site of the enzyme. IDH1 Arg132His (R132H) mutation can reduce the proliferative rate of glioma cells. Numerous diseases follow circadian rhythms, and there is growing evidence that circa‑ dian disruption may be a risk factor for cancer in humans. Dysregulation of the circadian clock serves an important role in the development of malignant tumors, including glioma. Brain‑Muscle Arnt‑Like protein 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) are the main biological rhythm genes. The present study aimed to further study whether there is an association between IDH1 R132H mutation and biological rhythm in glioma, and whether this affects the occurrence of glioma. The Cancer Genome Atlas (TCGA) database was used to detect the expression levels of the biological rhythm genes BMAL1 and CLOCK in various types of tumor. Additionally, U87‑MG cells were infected with wild‑type and mutant IDH1 lentiviruses. Colony forma‑ tion experiments were used to detect cell proliferation in each group, cell cycle distribution was detected by flow cytometry