Evaluation of the Oncogene Function of GOLPH3 and Correlated Regulatory Network in Lung Adenocarcinoma

Golgi phosphoprotein 3 (GOLPH3) is an oncoprotein localized in the Golgi apparatus. Abnormal GOLPH3 expression is potentially related to carcinogenesis. However, the potential biological regulation network of GOLPH3 in lung adenocarcinoma (LUAD) remains to be determined.

Upregulation of GOLPH3 has a positive correlation with clinicopathological subtypes and poor FP in LUAD. GOLPH3 promoted LUAD progression. Moreover, TUG1 may act as ceRNA to regulate GOLPH3 expression by competitive binding miR-142-5p.

Expression of GOLPH3 was identified in LUAD via TIMER, Oncomine, Lung Cancer Explorer (LCE), Human Protein Atlas (HPA), and UALCAN database. Survival analysis was performed using the Kaplan-Meier plotter. GOLPH3 alterations were analyzed through cBioPortal. LinkedOmics was used to perform functional analysis and predict interacted targets. The protein-protein interaction network was constructed by GeneMANIA. In addition, candidate miRNAs and lncRNAs targeting GOLPH3 were generated to construct competing endogenous RNA (ceRNA) network, and survival analysis of ceRNA was performed using LnCeVar. The mRNA or protein expression of TUG1, miR-142-5p, and GOLPH3 in Beas-2B and LUAD cells was verified using qPCR or Western blotting. CCK-8 assay, wound healing assay, and transwell assay were used to detect the ability of cell proliferation, migration, and invasion.

Overexpression of GOLPH3 was identified in LUAD. UALCAN analysis showed that upregulated GOLPH3 was linked to different pathological features of LUAD patients. Importantly, high GOLPH3 expression indicated a negative correlation with the first progression (FP) in LUAD patients. GOLPH3 alterations were also found. Moreover, co-expressed genes with GOLPH3 were analyzed; and they were involved in ribosome and oxidative phosphorylation pathways. Functional network analysis indicated GOLPH3 regulated T-cell receptor signaling pathway and interferon signaling pathway with kinase and transcription factor targets. Notably, TUG1/miR-142-5p/GOLPH3 affected overall survival of LUAD patients. GOLPH3 expression was decreased in the cells with overexpression of miR-142-5p and TUG1 knockdown. GOLPH3 reduction inhibited cell proliferation, migration, and invasion. Conclusions: Upregulation of GOLPH3 has a positive correlation with clinicopathological subtypes and poor FP in LUAD. GOLPH3 promoted LUAD progression. Moreover, TUG1 may act as ceRNA to regulate GOLPH3 expression by competitive binding miR-142-5p.