Circular RNA-hsa-circ-0000670 promotes gastric cancer progression through the microRNA-384/SIX4 axis.
Circular RNAs (circRNAs), a special type of non-coding RNA molecules, have been addressed to be implicated in gastric cancer progression. The GSE93541 and GSE83521 microarrays found hsa-circRNA-000670 (hsa-circ-0000670) as an up-regulated circRNAin gastric cancer. We mainly investigated the function and molecular mechanisms of hsa-circ-0000670 involved in gastric cancer. The expression of hsa-circ-0000670 was determined by RT-qPCR to be highly expressed in gastric cancer tissues relative to corresponding adjacent normal tissues, as well as in gastric cancer cell lines relative to normal gastric mucosal epithelial cell line. By conducting EdU, scratch test and Transwell assays, hsa-circ-000670 was found to be a tumor promoter by potentiating the proliferative, invasive and migrating capabilities of gastric cancer cells. Consistently, a tumor-promotive role of hsa-circ-000670 was validated in vivo. Dual-luciferase reporter gene and RIP assays identified the binding of hsa-circ-0000670 to microRNA-384 (miR-384) and the binding of miR-384 to sine oculis-related homeobox 4 (SIX4). The oncogenic potential of hsa-circ-0000670 in gastric cancer cells were inhibited by overexpressed miR-384. Mechanistically, SIX4 was targeted by miR-384 and was upregulated in gastric cancer. High SIX4 expression was suggested to correlate with the poor prognosis of gastric cancer patients. Additionally, silencing of SIX4 delayed tumor growth and progression, which were reversed by overexpression of hsa-circ-0000670. Taken together, hsa-circ-0000670 acts as a tumor promotor in gastric cancer progression and might be a potential target for gastric cancer treatment.
['Liu|Pengliang|P|', 'Cai|Shuang|S|', 'Li|Nuo|N|']
D000818:Animals D063646:Carcinogenesis D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D018450:Disease Progression D015536:Down-Regulation D015972:Gene Expression Regulation, Neoplastic D020868:Gene Silencing D018398:Homeodomain Proteins D006801:Humans D008297:Male D008819:Mice, Nude D035683:MicroRNAs D009361:Neoplasm Invasiveness D009857:Oncogenes D000079962:RNA, Circular D015398:Signal Transduction D013274:Stomach Neoplasms D015534:Trans-Activators D015854:Up-Regulation
Gastric cancer MicroRNA-384 Hsa-circ-0000670 Sine oculis-related homeobox 4