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Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis.
Molecular Oncology ( IF 5.0 ) Pub Date : 2020-02-13 , DOI: 10.1002/1878-0261.12638
Juan Jin 1 , Shanshan Xie 1, 2 , Qiang Sun 1 , Zhenxia Huang 1, 3 , Kanghua Chen 1 , Dongyang Guo 1 , Xianping Rao 1 , Yujie Deng 1 , Yiman Liu 1 , Shuang Li 1 , Wenyu Cui 1 , Valentina Chanu Maibam 1 , Junni Wang 1, 4 , Wei Zhuo 1, 5 , Tianhua Zhou 1, 5, 6, 7
Affiliation  

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.

中文翻译:

BCAM及其正义lncRNA BAN的上调与胃癌转移和预后不良有关。

转移性胃癌(GC)患者预后较差;然而,GC转移的分子机制仍不清楚。在这里,我们采用生物信息学系统地筛选了与转移相关的基因,发现与未转移的患者相比,转移患者的GC组织中基底细胞粘附分子(BCAM)的水平显着增加。BCAM的上调也与较短的生存时间显着相关。BCAM的耗竭抑制了GC细胞的迁移和侵袭。CRISPR / Cas9系统的BCAM敲除(KO)减少了GC细胞的侵袭和转移。为了探索BCAM上调的机制,我们鉴定了一个以前未表征的BCAM有义lncRNA,其范围从BCAM的外显子6到内含子6,并将其命名为BCAM相关的长非编码RNA(BAN)。敲除BAN可以抑制mRNA和蛋白质水平的BCAM表达。降低BAN抑制了GC细胞的迁移和侵袭,这可以通过异位表达BCAM有效地挽救。进一步的临床数据表明BAN上调与GC转移和预后不良有关。重要的是,GC组织中BAN的表达也与BCAM的表达显着相关。综上所述,这些结果表明,BCAM及其有义lncRNA BAN表达的增加促进了GC细胞的侵袭和转移,并与GC患者的预后不良有关。进一步的临床数据表明BAN上调与GC转移和预后不良有关。重要的是,GC组织中BAN的表达也与BCAM的表达显着相关。综上所述,这些结果表明,BCAM及其有义lncRNA BAN表达的增加促进了GC细胞的侵袭和转移,并与GC患者的预后不良有关。进一步的临床数据表明BAN上调与GC转移和预后不良有关。重要的是,GC组织中BAN的表达也与BCAM的表达显着相关。综上所述,这些结果表明,BCAM及其有义lncRNA BAN表达的增加促进了GC细胞的侵袭和转移,并与GC患者的预后不良有关。
更新日期:2020-01-17
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