Hsa_circ_0070661 inhibits cancer progression through miR-556-5p/TEK axis in lung adenocarcinoma

Abstract

BACKGROUND: Lung adenocarcinoma (LUAD) has a high incidence and poor prognosis, and multiple circRNAs (circRNAs) have been found to regulate LUAD. OBJECTIVE: This study focuses on the effect and mechanism of hsa_circ_0070661 in LUAD. METHODS: LUAD tissues and para-cancerous tissues were collected from 38 patients diagnosed with LUAD in our hospital. Hsa_circ_0070661, miR-556-5p and TEK Receptor Tyrosine Kinase (TEK) levels were evaluated using western blotting and RT-qPCR, and the targeting relationship was detected by luciferase reporter and RIP assays. Cell migration, viability, apoptosis-related proteins, (Bcl-2 and Bax) and tumor growth in vivo were assessed by Transwell, CCK-8, western blotting and xenograft assays, respectively. RESULTS: Results indicated downregulation of hsa_circ_0070661 and TEK in LUAD cell lines and tissues, whereas upregulation of miR-556-5p. Hsa_circ_0070661 upregulation restrained the viability, migration and tumor growth of LUAD cells, and promoted apoptosis. Hsa_circ_0070661 could directly target miR-556-5p to upregulate TEK expression in LUAD. MiR-556-5p upregulation promoted the malignant phenotypes of LUAD cells and reversed the anti-cancer effect of hsa_circ_0070661 overexpression, while TEK upregulation inhibited LUAD progression and somewhat eradicated the cancer-promoting effect of miR-556-5p upregulation. CONCLUSIONS: Hsa_circ_0070661 sponges miR-556-5p to inhibit LUAD development via regulating TEK, providing a promising molecular target for LUAD clinical therapy.

Non-coding RNAs as potential therapeutic targets for receptor tyrosine kinase signaling in solid tumors: current status and future directions

“…Several studies have investigated the association between circular RNA and receptor tyrosine kinase in lung adenocarcinoma. One study demonstrated that hsa_circ_0070661 suppressed cancer progression by regulating the miR-556-5p/TEK axis [ 187 ]. Li et al found that circ_0001058 inhibited lung adenocarcinoma development by modulating the miR-486-5p/TEK signaling pathway [ 188 ].…”