RASSF1A inhibits gastric cancer cell proliferation by miR-711- mediated downregulation of CDK4 expression

Abstract

Although interaction with DNA repair proteins has demonstrated that RASSF1A is a tumour suppressor gene, much attention has been directed in recent years towards its roles in regulating the cell cycle. However, the precise mechanism remains unclear. Uncovering how RASSF1A participates in regulating the cell cycle is critical to exploring effective therapeutic targets for gastric cancer. Here we show that RASSF1A could regulate 14 miRNAs’ expression in the typical human gastric cancer line SGC-7901, of which miR-711 was upregulated the most. Moreover, for SGC-7901 cells, miR-711 was found to downregulate CDK4 expression, and to arrest the cell cycle in the G1 phase. Our results suggest that RASSF1A inhibits the proliferation of gastric cancer cells by upregulating the expression of miR-711, which arrested gastric cancer cells in the G1 phase by downregulating expression of CDK4. This finding might provide us with a novel therapeutic target for gastric cancer by increasing RASSF1A expression via miR-711 regulation.

Long noncoding RNA gastric cancer-related lncRNA1 mediates gastric malignancy through miRNA-885-3p and cyclin-dependent kinase 4

“…Uncontrolled cell division, a core factor for cancer initiation, is mainly mediated by the imbalance of cell cycle machinery such as activation of cyclins and/or cyclin-dependent kinases (CDKs) 21 . Dysregulated cyclin or CDK activity is involved in almost all types of human cancers 20 , 22 – 29 . And the regulatory mechanisms of cyclins or CDKs in cancer oncogenesis and progression are also under exploration.…”

miR-34a targets BCL-2 to suppress the migration and invasion of sinonasal squamous cell carcinoma

“…Previous studies had reported that BCL-2 induced apoptosis of mitochondrial cells, indicating that BCL-2 played a role in tumor development by blocking apoptosis ( 19 ). BCL-2 expression was higher in multiple cancers and regulated by various miRNAs, such as pancreatic adenocarcinoma regulated by miR-126 ( 20 ), breast cancer regulated by miR-27a ( 21 ), gastric cancer by miR-711 ( 22 ), pancreatic cancer by miR-1180 ( 23 ). A previous study reported that BCL-2 expression was obviously increased in SN-SCC ( 24 , 25 ) and it is involved in the tumor cell proliferation, migration, invasion and apoptosis.…”

Inhibition of epithelial‑mesenchymal transition in gastric cancer cells by miR‑711‑mediated downregulation of CD44 expression

“…Because of the inconsistent findings, the biological functions of miR-711 remain unclear. In our previous study, we showed that the expression of miR-711 in gastric cancer tissues and cells was low, and that exogenous miR-711 expression inhibited gastric cancer cell invasion and migration by an unidentified mechanism (17). In this study, exogenous miR-711 overexpression in SGC-7901 or MGC-803 gastric cancer cells inhibited cancer cell invasion and migration.…”

“…In addition, we confirmed that the expression of miR-711 in gastric cancer tissues was also low. Further investigation demonstrated that miR-711 inhibited gastric cancer cell invasion and migration, however the mechanism was unclear (17). In the present study, we demonstrated that miR-711 regulated EMT of gastric cancer cells by downregulating CD44 expression both in vivo and in vitro.…”

“…These findings have demonstrated that miRNAs play a critical role in tumor development, progression and metastasis. The recent development of miRNA microarray analysis of gastric cancer has facilitated the identification of gastric cancer development-, progression-and prognosis-related miRNAs, and includes members of the miR-200 family, miR-27, miR-373, miR-148, miR-129 and miR-711 (12)(13)(14)(15)(16)(17). However, knowledge concerning these miRNAs only represent the tip of the iceberg, as the function of many miRNAs is still unknown.…”