Evaluation of hsa_circ_0000018/let-7f-5p/ FAM96A axis in lung adenocarcinoma progression.

Background: Circular RNAs (circRNAs) are critical regulators of lung adenocarcinoma (LA) progression. Although a molecular marker targeting hsa_circ_0000018 has been developed and used for diagnosing colon cancer, the role of this circRNA in LA progression has not been explored till now.

Objectives: This study aimed to elucidate the role and regulatory mechanisms of hsa_circ_0000018 in LA progression.

Methods: LA tissues and corresponding adjacent non-tumor tissues were collected from 36 patients to confirm the levels of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We also cultured two LA cell lines (A549, PC-9), and the human normal lung epithelial cell line BEAS-2B. Cell function experiments were conducted to assess malignancy in LA cells, including proliferation, migration, and invasion, following forced hsa_circ_0000018 expression. The correlation between hsa_circ_0000018, let-7f-5p, and family with sequence similarity 96 member A (FAM96A) was confirmed by using starBase (miRNA-circRNA interaction database), luciferase assay, and western blotting.

Results: Expression of hsa_circ_0000018 and FAM96A was reduced, whereas that of let-7f-5p was upregulated in LA. Cell function assays revealed that upregulation of hsa_circ_0000018 had a suppressive effect on the proliferation, migration, and invasion of LA cells. Additionally, hsa_circ_0000018 sponge binds let-7f-5p, resulting in upregulation of FAM96A expression.

Conclusion: Our data reveal hsa_circ_0000018 as a tumor suppressor in LA that targets the let-7f-5p/FAM96A axis. Our findings enrich the known regulatory network of circRNAs in LA.