No abstract

Emerging evidence suggests that altered expression of microRNAs (miRNAs) is involved in cancer progression. However, the role of miR-125a-5p in gastric carcinogenesis remains unknown. Quantitative real-time PCR analysis revealed that the expression of miR-125a-5p was significantly decreased in >80% of gastric cancer tissues compared with their adjacent non-tumor tissues, and was markedly reduced in ~95% of intestinal-type gastric cancer tissues. The downregulated miR-125a-5p was significantly associated with gastric cancer metastasis. Ectopic expression of miR-125a-5p substantially inhibited the proliferation, migration and invasion activities of gastric cancer cells. Furthermore, forced expression of miR-125a-5p repressed the activity of a luciferase reporter carrying the 3'-untranslated (3'-UTR) region of E2F3, which was eliminated by mutation of the predicted miR-125a-binding site, indicating that E2F3 may be a potential target gene of miR-125a-5p. These data suggest that by targeting E2F3, miR-125a-5p may be important as a potential tumor suppressor gene in gastric carcinogenesis.

MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2.

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.