Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis.

Juan Jin,Xianping Rao,Tianhua Zhou,Yiman Liu,Shuang Li,Zhenxia Huang,Wei Zhuo,Shanshan Xie,Valentina Chanu Maibam,Junni Wang,Yujie Deng,Dongyang Guo,Kanghua Chen,Wenyu Cui,Qiang Sun

doi:10.1002/1878-0261.12638

Abstract

Patients with metastatic gastric cancer (GC) have a poor prognosis; however, the molecular mechanism of GC metastasis remains unclear. Here, we employed bioinformatics to systematically screen the metastasis‐associated genes and found that the levels of basal cell adhesion molecule (BCAM) were significantly increased in GC tissues from patients with metastasis, as compared to those without metastasis. The upregulation of BCAM was also significantly associated with a shorter survival time. Depletion of BCAM inhibited GC cell migration and invasion. Knockout (KO) of BCAM by the CRISPR/Cas9 system reduced the invasion and metastasis of GC cells. To explore the mechanism of BCAM upregulation, we identified a previously uncharacterized BCAM sense lncRNA that spanned from exon 6 to intron 6 of BCAM, and named it as BCAM‐associated long noncoding RNA (BAN). Knockdown of BAN inhibited BCAM expression at both mRNA and protein levels. Knockdown of BAN suppressed GC cell migration and invasion, which was effectively rescued by ectopic expression of BCAM. Further clinical data showed that BAN upregulation was associated with GC metastasis and poor prognosis. Importantly, BAN expression was also significantly associated with that of BCAM in GC tissues. Taken together, these results indicate that increased expression of BCAM and its sense lncRNA BAN promote GC cell invasion and metastasis, and are associated with poor prognosis of GC patients.

Highlights

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and is the third leading cause of cancer-related deaths worldwide (Bray et al, 2018)
We found that Basal cell adhesion molecule (BCAM) expression was significantly correlated with GC metastasis and poor prognosis
We identified a previously undescribed gene BCAM-associated long noncoding RNA (lncRNA) (BAN) as a sense lncRNA of BCAM, which was associated with GC metastasis and poor prognosis

Summary

Introduction

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and is the third leading cause of cancer-related deaths worldwide (Bray et al, 2018). Due to the lack of obvious symptoms and biomarkers for earlystage GC, ~ 40% of GC patients present with metastasis at the time of diagnosis (Bernards et al, 2013). The overall survival of GC patients with metastasis is poor, with an about 5% of the 5-year survival rate (Bernards et al, 2013). Emerging studies have shown that BCAM plays an important role in tumor progression, including skin tumors, hepatocellular carcinoma, colorectal cancer, and bladder cancer (Bartolini et al, 2016; Campbell et al, 1994; Chang et al, 2017; Drewniok et al, 2004; Kikkawa et al, 2013). The role of BCAM in GC progression is still unclear

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Results

Conclusion