title: Angiogenin promotes U87MG cell proliferation by activating NF-κB signaling pathway and downregulating its binding partner FHL3.
abstract: Angiogenin (Ang) is known to induce cell proliferation and inhibit apoptosis by cellular signaling pathways and its direct nuclear functions, but the mechanism of action for Ang in astrocytoma is not yet clear. Astrocytoma is the most frequent one among various neurogliomas, of which a subtype known as glioblastoma multiforme (GBM) is the most malignant brain glioma and seriously influences the life quality of the patients. The expression of Ang and Bcl-xL were detected in 28 cases of various grades of astrocytoma and 6 cases of normal human tissues by quantitative real-time PCR. The results showed that the expression of Ang and Bcl-xL positively correlated with the malignant grades. Cytological experiments indicated that Ang facilitated human glioblastoma U87MG cell proliferation and knock-down of endogenous Ang promoted cell apoptosis. Furthermore, Ang activated NF-κB pathway and entered the U87MG cell nuclei, and blocking NF-κB pathway or inhibiting Ang nuclear translocation partially suppressed Ang-induced cell proliferation. The results suggested that Ang participated in the regulation of evolution process of astrocytoma by interfering NF-κB pathway and its nucleus function. In addition, four and a half LIM domains 3 (FHL3), a novel Ang binding partner, was required for Ang-mediated HeLa cell proliferation in our previous study. We also found that knockdown of FHL3 enhanced IκBα phosphorylation and overexpression of Ang inhibited FHL3 expression in U87MG cells. Together our findings suggested that Ang could activate NF-κB pathway by regulating the expression of FHL3. In conclusion, the present study established a link between Ang and FHL3 proteins and identifies a new pathway for regulating astrocytoma progression.
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Wenrong
authors: W
authors: Xia
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Wenliang
authors: W
authors: Fu
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Xin
authors: X
authors: Cai
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Min
authors: M
authors: Wang
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Huihua
authors: H
authors: Chen
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Weiwei
authors: W
authors: Xing
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Yuanyuan
authors: Y
authors: Wang
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Minji
authors: M
authors: Zou
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Tao
authors: T
authors: Xu
authors: Laboratory of Genome Engineering, Beijing Institute of Basic Medical Sciences, Beijing, PR China.
authors: Donggang
authors: D
authors: Xu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C117563:FHL3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic