The putative tumor suppressor microRNA-497 modulates gastric cancer cell proliferation and invasion by repressing eIF4E.
Accumulating evidence has shown that microRNAs are involved in multiple processes in gastric cancer (GC) development and progression. Aberrant expression of miR-497 has been frequently reported in cancer studies; however, the role and mechanism of its function in GC remains unknown. Here, we reported that miR-497 was frequently downregulated in GC tissues and associated with aggressive clinicopathological features of GC patients. Further in vitro observations showed that the enforced expression of miR-497 inhibited cell proliferation by blocking the G1/S transition and decreased the invasion of GC cells, implying that miR-497 functions as a tumor suppressor in the progression of GC. In vivo study indicated that restoration of miR-497 inhibited tumor growth and metastasis. Luciferase assays revealed that miR-497 inhibited eIF4E expression by targeting the binding sites in the 3'-untranslated region of eIF4E mRNA. qRT-PCR and Western blot assays verified that miR-497 reduced eIF4E expression at both the mRNA and protein levels. A reverse correlation between miR-497 and eIF4E expression was noted in GC tissues. Taken together, our results identify a crucial tumor suppressive role of miR-497 in the progression of GC and suggest that miR-497 might be an anticancer therapeutic target for GC patients.
Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China.
Weidong
W
Li
Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China.
Xuejun
X
Jin
Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China.
Xubin
X
Deng
Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, People's Republic of China.
Gong
G
Zhang
Cancer Research Institution, Southern Medical University, Guangzhou, People's Republic of China.
Bingqian
B
Zhang
Department of Medical Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China. Electronic address: malei01@yeah.net.
Lei
L
Ma
D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D020413:3' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm
Gastric cancer; MiR-497; eIF4E