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

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.

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

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.

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.

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.