Laboratory of Veterinary Radiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka, 598-8531, Japan.
Laboratory of Veterinary Radiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka, 598-8531, Japan.
Exp Cell Res. 2021 Mar 15;400(2):112504. doi: 10.1016/j.yexcr.2021.112504. Epub 2021 Jan 27.
Canine glioma is a common brain tumor with poor prognosis despite surgery and/or radiation therapy. Therefore, newer and more effective treatment modalities are needed. Neuregulin 3 (NRG3) has known to be a ligand of ERBB4. This study aimed to investigate the usefulness of the NRG3/ERBB4 signaling cascade as a novel therapeutic target in canine glioma. We found out that microRNA (miR)-190a was downregulated in canine brain tumor tissues, including glioma and meningioma. miR-190a directly targeted NRG3 and inhibited the growth of canine glioma cells. The level of p-Akt, which is a downstream target of ERBB4 signaling, was decreased by transfection with miR-190a. NRG3 silencing also suppressed cell growth and decreased the levels of p-Akt and p-ERK1/2, and NRG3 overexpression exhibited opposed effects in canine glioma J3T-1 cells. The mRNA level of erbb4 was significantly upregulated in glioma tissues compared with that in normal brain tissues and meningioma tissues. Furthermore, compared with gefitinib and lapatinib, afatinib exerted a greater inhibitory effect on the growth of canine glioma cells. In conclusion, NRG3/ERBB4 signaling is negatively regulated by miR-190a and contributes to the growth of canine glioma cells, indicating that it may be a promising therapeutic target in canine glioma.
犬脑胶质瘤是一种常见的脑肿瘤，尽管进行了手术和/或放射治疗，但预后仍不佳。因此，需要新的、更有效的治疗方法。神经调节蛋白 3（NRG3）已知是 ERBB4 的配体。本研究旨在探讨 NRG3/ERBB4 信号级联作为犬脑胶质瘤新的治疗靶点的有用性。我们发现 microRNA（miR）-190a 在犬脑肿瘤组织中（包括神经胶质瘤和脑膜瘤）下调。miR-190a 直接靶向 NRG3 并抑制犬神经胶质瘤细胞的生长。转染 miR-190a 后，ERBB4 信号的下游靶标 p-Akt 的水平降低。NRG3 沉默也抑制细胞生长并降低 p-Akt 和 p-ERK1/2 的水平，NRG3 过表达在犬神经胶质瘤 J3T-1 细胞中表现出相反的作用。与正常脑组织和脑膜瘤组织相比，神经胶质瘤组织中 erbb4 的 mRNA 水平显著上调。此外，与吉非替尼和拉帕替尼相比，阿法替尼对犬神经胶质瘤细胞的生长具有更大的抑制作用。总之，NRG3/ERBB4 信号受 miR-190a 的负调控，有助于犬神经胶质瘤细胞的生长，表明它可能是犬神经胶质瘤有前途的治疗靶点。
