Article Abstract

Up-regulated GGA3 promotes non-small cell lung cancer proliferation by regulating TrkA receptor

Authors: Bo-Gang Jiang, Yan-Rong Zhou

Abstract

Background: GGA3 has been reported to be related to cellular events such as cell survival, cell migration and cell apoptosis through different molecular mechanisms, which imply the potential role in tumorigenesis. However, the function of GGA3 in non-small cell lung cancer (NSCLC) is not clear. This research aims to reveal the effect of GGA3 on NSCLC proliferation and its underlying mechanisms.
Methods: The mRNA expression of GGA3 and TrkA, and association between GGA3 and TrkA in NSCLC tissues were analyzed based on data from TCGA database. And the mRNA expression level of GGA3 in NSCLC cell lines was determined by qRT-PCR. Expression level of GGA3 in A549 cell was detected by qRT-PCR and western blot after transfected with pcDNA3.1-GGA3. Cell counting kit 8, transwell, and flow cytometry assays were performed to detect A549 cell proliferation, aggressiveness, and apoptosis. Western blot was applied to assess the protein expression during apoptosis and TrkA-AKT/ERK signaling pathway.
Results: High expression of GGA3 was presented in NSCLC tissues and cell lines. In addition, overexpression of GGA3 could promote proliferation, invasion, and migration of A549 cell, but inhibit the apoptosis of A549 cell. After depletion of GGA3, the expression of anti-apoptotic protein Bcl-2 was increased, and the expression of pro-apoptotic protein Bax and Active Caspase 3 were reduced. Moreover, we found the expression of TrkA, p-AKT and p-ERK in pcDNA3.1-GGA3 group were obviously up-regulated in contrast with the sham group, which suggested that the induced effect of GGA3 on NSCLC cells might be performed via the TrkA-AKT/ERK signaling pathway.
Conclusions: Taken together, overexpressed GGA3 in NSCLC could promote the A549 cells tumorigenesis partly through TrkA-AKT/ERK signaling pathway, supplying a theoretical basis for revealing the mechanism for NSCLC.

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