Circular RNA-hsa-circ-0000670 promotes gastric cancer progression through the microRNA-384/SIX4 axis

• DOI: 10.1016/j.yexcr.2020.112141
• Publication Date: 2020-06-11T16:19:19Z
• Authors: Pengliang Liu; Shuang Cai; Nuo Li
• Keywords: Homeodomain Proteins; Male; 0303 health sciences; Carcinogenesis; Down-Regulation; Mice, Nude; Oncogenes; RNA, Circular; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Movement; Stomach Neoplasms; Cell Line, Tumor; Disease Progression; Trans-Activators; Animals; Humans; Neoplasm Invasiveness; Gene Silencing; Cell Proliferation; Signal Transduction

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.