LTBP2 silence suppresses glioblastoma proliferation and tumor growth of xenograft tumor mice through modulating JAK2/STAT2 signaling pathway

Abstract

Glioblastoma is considered the most malignant central nervous system tumor. This study aimed to investigate effects of latent transforming growth factor-β binding protein-2 (LTBP2) on glioblastoma growth and associated mechanisms. LTBP2 gene transcription in glioblastoma was determined using RT-PCR. LTBP2 gene silencing lentiviral vectors were synthesized, and the highest efficient vector was selected to package sh-LTBP2 lentivirus. Xenograft tumor model was constructed by injecting sh-LTBP2-infected U87MG cells into mice, and tumor growth was evaluated. Proliferation, colony formation and migration of U87MG were verified with CCK-8, colony-formation assay and migration assay, and cell cycle was examined. Western blot and immunohistochemistry were performed to examine Janus kinase 2 (JAK2) and signal transducers and activators of transcription 2 (STAT2) phosphorylation. LTBP2 gene transcription in SVGp12 cells was significantly lower compared to U87MG, U251 and T98G cells (P < 0.001). LTBP2 gene silence suppressed U87MG cell proliferation, migration and colony formation compared to U87MG group and sh-NC group (P < 0.05). LTBP2 gene silence regulated phases of cell cycle in U87MG cells. JAK2/STAT2 participated in LTBP2 silence-induced decreased U87MG proliferation. LTBP2 gene silence suppressed tumor growth by modulating JAK2/STAT2 pathway in xenograft tumor mice. In conclusion, LTBP2 silence inhibited proliferation and migration of U87MG cells and tumor growth of xenograft tumor mice through modulating JAK2/STAT2 signaling pathway.

Keywords: Gene silence; Glioblastoma; JAK2/STAT2 pathway; LTBP2; Tumor growth.