Abstract
Glycosyltransferases are frequently dysregulated in lung cancer. Core 1 β 1, 3-galactosyltransferase 1 (C1GALT1), an enzyme highly expressed in various cancers, is correlated with tumor initiation and development. However, the role of C1GALT1 in lung cancer remains poorly understood. In this study, through bioinformatic analysis and clinical validation, we first discovered that C1GALT1 expression was upregulated in lung adenocarcinoma (LUAD) tissues and was closely related to poor prognosis in patients with LUAD. Gain- and loss-of-function experiments showed that C1GALT1 promoted LUAD cell proliferation, migration, and invasion in vitro, as well as tumor formation in vivo. Further investigation demonstrated that RAC1 expression was positively regulated by C1GALT1 in LUAD, whereas silencing Rac1 could reverse C1GALT1-induced tumor growth and metastasis. Moreover, miR-181d-5p was identified as a negative regulator for C1GALT1 in LUAD. As expected, the inhibitory effects of miR-181d-5p on LUAD cell proliferation, migration, and invasion were counteracted by restoration of C1GALT1. In summary, our results highlight the importance of the miR-181d-5p/C1GALT1/RAC1 regulatory axis during LUAD progression. Thus, C1GALT1 may serve as a potential therapeutic target for LUAD.
Highlights
According to the global cancer statistics in 2018, lung cancer remains the most frequent cancer and the leading cause of cancer death worldwide (Bray et al, 2018)
We found that C1GALT1 was overexpressed in lung adenocarcinoma (LUAD) tissues and high C1GALT1 expression was associated with poor prognosis in LUAD patients
C1GALT1 Is Overexpressed in LUAD and Predicts Poor Prognosis
Summary
According to the global cancer statistics in 2018, lung cancer remains the most frequent cancer and the leading cause of cancer death worldwide (Bray et al, 2018). NSCLC is further classified into three types, namely, lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and large cell carcinoma. Role of C1GALT1 in LUAD radiotherapy, and immunotherapy) have been applied for the treatment of lung cancer, some patients still develop postoperative recurrence and metastasis. Frequent recurrence or metastasis remains a major obstacle for lung cancer treatment (Wang et al, 2019; Zhan et al, 2019). It is essential to clarify the mechanism underlying the pathogenesis and progression of lung cancer, which may help to improve therapeutic outcomes
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