Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis
Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis
复制标题
BCAM及其正义lncRNA BAN的上调与胃癌转移和不良预后相关
DOI：
10.1002/1878-0261.12638
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发表时间：
2020-02-13
影响因子：
6.6
通讯作者：
Zhou, Tianhua
中科院分区：
文献类型：
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作者：
Jin, Juan;Xie, Shanshan;Zhou, Tianhua
转移性胃癌（GC）患者预后差，然而，GC转移的分子机制仍不清楚。在此，我们采用生物信息学系统筛选转移相关基因，发现基底细胞粘附分子（BCAM）的水平显着增加，从胃癌组织中转移的患者，与那些没有转移。BCAM的上调也与较短的生存时间显著相关。BCAM的耗竭抑制了GC细胞的迁移和侵袭。通过CRISPR/Cas9系统敲除（KO）BCAM降低了GC细胞的侵袭和转移。为了探索BCAM上调的机制，我们鉴定了一种以前未表征的BCAM正义lncRNA，其跨越BCAM的外显子6至内含子6，并将其命名为BCAM相关长非编码RNA（BAN）。BAN的敲除在mRNA和蛋白水平上抑制BCAM的表达。BAN的敲除抑制了GC细胞的迁移和侵袭，而BCAM的异位表达有效地挽救了这一点。进一步的临床资料显示BAN表达上调与胃癌转移和预后不良有关。更重要的是，BAN的表达也与BCAM在GC组织中的表达显著相关。综上所述，这些结果表明，BCAM及其正义lncRNA BAN的表达增加促进GC细胞的侵袭和转移，并且与GC患者的不良预后相关。
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.