Long non-coding RNA CCAL/miR-149/FOXM1 axis promotes metastasis in gastric cancer

Abstract

Early evidence indicates that the long non-coding RNA CCAL plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of CCAL in gastric tumourigenesis and progression remain largely unknown. We observed that CCAL was upregulated in gastric cancer tissues and was associated with the tumour-node-metastasis stage. Functional experiments showed that CCAL promoted gastric cancer cell proliferation and metastasis in vitro and in vivo. Luciferase reporter assay indicated that CCAL directly bind to miR-149. Moreover, knockdown of CCAL significantly reduced the expression of FOXM1, a direct target of miR-149. We also showed that FOXM1 suppression by miR-149 could be partially rescued by CCAL overexpression. In addition, we identified a negative correlation between the mRNA expression of CCAL and miR-149 in gastric cancer tissues. Furthermore, we observed a negative correlation between the expression of miR-149 and FOXM1 and a positive correlation between CCAL and FOXM1 levels. These results demonstrated that the CCAL/miR-149/FOXM1 axis functions as a key regulator in gastric cancer metastasis and CCAL potentially represents a biomarker for diagnosis and potential target for therapy in the future.

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF

“…Although the early diagnosis and therapy of GC were rapidly developed over the past decades, most of the patients with GC were faced with metastasis recurrence [31][32][33]. It is important for GC patients to search out effective new biomarkers.…”

Hsa_circ_0017728 as an oncogene in gastric cancer by sponging miR-149 and modulating the IL-6/STAT3 pathway

“…However, the luciferase activity had no significant change when the corresponding target sites were mutated in MKN-28 and MGC-803 cells (Figures 4 C, D). In addition, we found that miR-149 was down-regulated in human GC tissues compared with that in the corresponding non-cancerous tissues (Figure 4 MiR-149 exerted an anti-oncogenic effect in vitro by targeting IL-6/STAT3 signaling miR-149 as an anti-oncomiR has been reported during GC tumorigenesis [19]. Interestingly, IL-6 is a direct target involved in miR-149-associated oncotherapy [24,29].…”

“…We also found that the expression of miR-149 was significantly and negatively correlated with hsa_circ_0017728 in GC tissues, suggesting that miR-149 exerted a negative function with hsa_circ_0017728 in the progression of GC. Previous studies have reported the miR-149 primarily serves as an anti-tumor miRNA, and its expression levels are repressed in multiple types of cancers, including HCC [34], breast cancer [35] and GC [19]. Luo et al showed that over-expression of miR-149 suppresses HCC cell migration and invasion in vitro [34].…”

“…Luo et al showed that over-expression of miR-149 suppresses HCC cell migration and invasion in vitro [34]. Luo et al suggested that overexpression of miR-149 impairs the migration and invasion ability of HGC-27 and SGC-7901 cells [19]. Chan et al stated that overexpression of miR-149 has no effect on cell proliferation in IV2 and Hs578T cells, but suppressed cell migration and invasion in vitro and metastasis in vivo [35].…”

“…miR-149, as one of the most well-characterized anti-oncomiRs, is reduced in a variety of cancers and cell lines, including bladder cancer, colorectal cancer and breast cancer [16][17][18]. In GC, lncRNAs as ceRNAs contain conserved miRNA binding sites and recruit miR-149 to the inactivation of their expression and the reinforcement of their downstream targets, which result in the acceleration of cell proliferation and metastasis [19,20].…”