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

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.

Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells

“…Down‐regulated proteins integrin subunit alpha 2 (ITGA2) and unconventional myosin 1G (MYO1G) (both involved in leukocyte migration), cysteine‐rich 61 (CCN1) (ECM‐protein regulating cell adhesion), CD59 and CD55 (integrins involved in complement cascade activation) (Figure 2C). Most of the aforementioned proteins have been implicated with poor prognosis and metastasis in gastro‐intestinal cancers [105–109].…”

“…BCAM is a member of the immunoglobulin superfamily and a receptor for the ECM protein laminin. Interestingly, BCAM levels are significantly higher in primary GC tumors of patients with metastasis and predict a worse overall survival and increase cell migration, invasion and metastasis by mediating tumor-ECM interactions [105,138]. COL3A1 is a type III collagen and part of the interstitial matrix regulating stromal components and is up-regulated in GC versus normal stomach tissue and is a marker of poor prognosis in many cancer types [106,107,139,140].…”

Cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment

“…BCAM is known to interact through its ligand LAMA5 , a component of the laminin-511 heterotrimer found within the placental extracellular matrix 47,48 . BCAM was identified as an antigen upregulated in ovarian carcinoma, and has been described to facilitate tumor migration by competing for laminin binding with integrins in the basement membrane, as well as cell-cell adhesion 49,50 , designating BCAM as an important oncogene 51 . Here, flow cytometric sorting of BCAM hi and BCAM lo CTBs for organoid colony formation demonstrates that BCAM hi cells have a significantly improved capacity for trophoblast organoid growth.…”

Long Noncoding RNA LIT3527 Knockdown induces Apoptosis and Autophagy through inhibiting mTOR pathway in Gastric Cancer Cells

“…Cells were lysed using RIPA protein extraction reagent (Beyotime, China) supplemented with a protease inhibitor cocktail (Roche, USA). Western blotting was carried out as previously reported [17]. The proteins were detected using anti-LC3B antibody (Cell Signaling, USA), anti-4EBP1 antibody (Cell Signaling, USA), anti-mTOR antibody (Cell Signaling, USA), anti-p-mTOR antibody (Cell Signaling, USA), anti-Akt antibody (Diagbio, China), anti-p-Akt antibody (Diagbio, China), anti-Erk antibody (Diagbio, China), anti-p-Erk antibody (Diagbio, China), anti-GAPDH antibody (Sigma-Aldrich, USA) and corresponding secondary antibodies.…”