Inhibition of translocator protein 18 kDa suppressed the progression of glioma via the ELAV-like RNA-binding protein 1/MAPK-activated protein kinase 3 axis

• Published in: Bioengineered Vol. 13; no. 3; pp. 7457 - 7470
• Main Authors: Wang, Jingya, Ren, Peng, Zeng, Zhirui, Ma, Li, Li, Yunjun, Zhang, Hongmei, Guo, Wenzhi
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.03.2022
• Subjects: Adult; Cell Line, Tumor; ELAV-Like Protein 1 - genetics; ELAV-Like Protein 1 - metabolism; Gene Expression Regulation, Neoplastic; Glioma; Glioma - metabolism; Humans; HUR; MAPKAPK3; mobility; proliferation; Protein Kinases - genetics; Protein Kinases - metabolism; Protein Kinases - therapeutic use; Receptors, GABA - genetics; Receptors, GABA - metabolism; Receptors, GABA - therapeutic use; Research Paper; RNA-Binding Proteins - metabolism; TSPO; TSPO; mobility; Glioma; HUR; MAPKAPK3; proliferation
• DOI: 10.1080/21655979.2022.2048992
• ISSN: 2165-5979

Glioma is the most common primary malignant brain tumors in adults. Despite considerable advances in treatment, the clinical outcome remains dismal. Translocator protein 18 kDa (TSPO), an evolutionarily conserved transmembrane protein, has always been found to be elevated in glioma, which predicts a poor prognosis. However, studies on the regulatory network of TSPO in glioma are limited. The Cancer Genome Atlas (TCGA) and our research group cohorts demonstrated that TSPO expression was also highly expressed in glioma tissues and glioma cell lines. Inhibition of TSPO expression significantly reduced glioma cell proliferation and mobility in vitro. Suppression of TSPO decreased the expression of MAPK-activated protein kinase 3 (MAPKAPK3) and increased the degradation rate of its mRNA. TSPO directly interacts with ELAV1-like RNA-binding protein 1 (HUR) and promotes the nuclear-cytoplasmic shuttling of HUR. Inhibition of HUR decreased MAPKAPK3 expression and cell proliferation and mobility, whereas overexpression of MAPKAPK3 reversed the effects. Overexpression of HUR in TSPO-knockdown cells enhanced the mRNA stability of MAPKAPK3. Furthermore, rescue experiments show that the HUR/MAPKAPK3 axis accounts for the TSPO-mediated effects on glioma cell proliferation and mobility. Together, our present study indicated that TSPO may promote the nuclear-cytoplasmic shuttling of HUR, thus increasing the mRNA stability of MAPKAPK3 and promoting the proliferation and mobility of glioma cells. The HUR/MAPKAPK3 axis may be key targets for blocking the effects of TSPO and may contribute to glioma therapy.