RESUMEN
Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.
Asunto(s)
MicroARNs , ARN Circular , Proteína de Replicación C , Neoplasias Gástricas , Ubiquitina Tiolesterasa , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , MicroARNs/genética , ARN Circular/genética , Proteína de Replicación C/genética , Proteína de Replicación C/metabolismo , Neoplasias Gástricas/patología , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , UbiquitinaciónRESUMEN
Gastric cancer (GC) has been recognized as the major reason for global cancer-associated mortality. SEC62 homolog, preprotein translocation factor (SEC62) has been documented to possess carcinogenic functions in cancers, but its influence on GC remains elusive. Present study aimed to uncover the impact and mechanism of SEC62 in GC. We validated the upregulation of SEC62 in GC samples by GEPIA, and revealed its high level in GC cell lines. Functionally, depletion of SEC62 hindered proliferation and encouraged apoptosis in GC cells. Furthermore, we found through Starbase 3.0 and validated that methyltransferase like 3 (METTL3) interacted with SEC62 to induce the m6A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2 binding protein 1 (IGF2BP1) on SEC62 mRNA. Moreover, we predicted through miRmap and validated that miR-4429 targeted and inhibited METTL3 to repress SEC62. Rescue assays demonstrated that miR-4429 inhibited GC progression through METTL3/SEC62 axis. Together, our study firstly revealed that miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m6A-caused stabilization of SEC62, indicating miR-4429 as a promising target for treatment improvement for GC.
