ERK-CREB pathway is involved in HSPB8-mediated glioma cell growth and metastatic properties

Exp Mol Pathol. 2021 May 24:104653. doi: 10.1016/j.yexmp.2021.104653. Online ahead of print.

Abstract

Objective: To investigate the mechanism of HSPB8 (heat shock protein beta-8) in the growth and metastatic properties of glioma cells.

Methods: HSPB8 expression in glioma tissue and cell was detected via Western blotting. Then, glioma U87 and U251 cell lines were divided into Mock group, Control siRNA group, HSPB8 siRNA-1 group and HSPB8 siRNA-2 group. Cell proliferation was detected using MTT assay, while its invasion, migration and apoptosis were determined by Transwell, wound-healing and flow cytometry, respectively. The expression of HSPB8 and ERK-CREB pathway-related molecules were also measured by Western blotting. Xenograft models were constructed on nude mice, and accordingly, the growth curve of subcutaneous xenograft was prepared.

Results: In glioma tissues, HSPB8 expression was upregulated with the increasing grade of glioma. Besides, glioma cells in the HSPB8 siRNA-1 group and HSPB8 siRNA-2 group manifested the significant enhancement in apoptotic rates and reductions in its proliferation, migration and invasion compared to those in the Mock group, meanwhile, the expression of HSPB8, p-ERK1/2/ERK1/2 and p-CREB/CREB were downregulated. On the other hand, the tumor growth in the nude mice of Ad-HSPB8 shRNA-1 group and Ad-HSPB8 shRNA-2 group was retarded significantly, with an acute decrease in the tumor weight.

Conclusion: Silencing HSPB8 can inhibit the malignant features, while facilitate the apoptosis of glioma cells, with inactivation of ERK-CREB pathway.

Keywords: ERK-CREB signaling pathway; Glioma; HSPB8.