Overexpression of hsa_circ_0008274 inhibited the progression of lung adenocarcinoma by regulating HMGA2 via sponging miR-578

Abstract

Background: Circular RNAs (circRNAs) had been identified as a non-coding RNA associated with many types of cancer in recent years. However, the involvement of hsa_circ_0008274 in lung adenocarcinoma (LUAD) has not been explored. The aim of our research is to explore the biological mechanism and function of hsa_circ_0008274 in LUAD.

Methods: The hsa_circ_0008274, miR-578, and high mobility group AT-Hook 2 (HMGA2) mRNA expression levels were detected via qRT-PCR. Cell Counting Kit-8 (CCK-8) Transwell assay and wound healing assay were performed to measure the cell proliferation, invasion, and migration ability. Luciferase reporter and Western blotting experiments were performed to characterize the competing endogenous RNA (ceRNA) mechanism of hsa_circ_0008274.

Results: Our findings determined that the expression of hsa_circ_0008274 in LUAD was significantly decreased. Cell experiments showed that overexpressed hsa_circ_0008274 could reduce the proliferation and invasion ability of LUAD cells. Moreover, miRNA-578 could identify as a miRNA sponge of hsa_circ_0008274. Overexpressed hsa_circ_0008274 reduced the proliferation and invasion of LUAD cells caused by miR-578 mimics. Increasing the expression of miR-578 can aggravate the proliferation and invasion of LUAD cells and block the inhibition of proliferation and invasion of LUAD cells mediated by overexpressed hsa_circ_0008274. Subsequent data indicate that HMGA2 of the tumor-promoting gene is the target gene of miR-578. The upregulation of HMGA2 partially reversed the tumor inhibitory effect of LUAD cells induced by overexpressed hsa_circ_0008274 or miR-578 mimics.

Conclusions: In summary, our data show that the overexpression of hsa_circ_0008274 repressed the proliferation and invasion of LUAD through downregulating miR-578 and activating HMGA2.

Keywords: HMGA2; hsa_circ_0008274; lung adenocarcinoma; miR-578.