Ubiquitin Conjugating Enzyme E2 H (UBE2H) Is Linked to Poor Outcomes and Metastasis in Lung Adenocarcinoma

SIMPLE SUMMARY: The development of novel treatments for metastatic lung adenocarcinoma is an important issue because some patients do not respond to current standard therapies. Our study aimed to investigate the gene expression profiles in non-tumor tissue, primary tumor tissue, and the metastatic lung tumor tissue in the pleura. After RNA sequencing and bioinformatic analysis from a patient with lung adenocarcinoma (LUAD), ubiquitin conjugating enzyme E2 H (UBE2H) was identified. Compared with normal tissue, a higher expression of UBE2H was observed in the tumor tissue. The high UBE2H expression was significantly associated with poor survival. Suppressing UBE2H in cell lines of lung adenocarcinoma inhibited metastatic capacity and reversed epithelial–mesenchymal transition signaling pathway. Five microRNAs, including miR-101, miR-30a, miR-30b, miR-328, and miR-497, predicted to target UBE2H might be potential prognostic biomarkers for survival in lung adenocarcinoma. The copy number variation may be involved in the regulation of the UBE2H expression. Our observations show that UBE2H is a novel regulatory molecule of metastasis, and may be a prognostic biomarker and a therapeutic target in lung adenocarcinoma. ABSTRACT: The prognosis of patients with metastatic lung adenocarcinoma (LUAD) is poor. Although novel lung cancer treatments have been developed for metastatic LUAD, not all patients are fit to receive these treatments. The present study aimed to identify the novel regulatory genes in metastatic LUAD. Because the pleural cavity is a frequent metastasis site of LUAD, the adjacent non-tumor tissue, primary tumor tissue, and metastatic lung tumor tissue in the pleura of a single patient with LUAD were collected. The gene expression profiles of the collected samples were further analyzed via RNA sequencing and bioinformatic analysis. A high expression level of ubiquitin conjugating enzyme E2 H (UBE2H), a hypoxia-mediated gene, was identified in the metastatic malignant pleural tumor. After accessing the survival data in patients with lung adenocarcinoma through online databases, a high UBE2H expression was associated with poor survival for LUAD. UBE2H knockdown in two lung adenocarcinoma cell lines suppressed the cell migration capacity and reversed the epithelial–mesenchymal transition (EMT) signaling pathway. A high expression of UBE2H-targeting microRNAs, including miR-101, miR-30a, miR-30b, miR-328, and miR-497, were associated with a favorable prognosis. Moreover, the UBE2H expression revealed a significant correlation with the copy number variation. Taken together, the presence of UBE2H regulated the EMT program and metastasis in LUAD.