Circular RNA _0015278 inhibits the progression of non-small cell lung cancer through regulating the microRNA 1278/SOCS6 gene axis

Yiwang Ye; Xuan Wu; Feihu Long; Wei Yue; Da Wu; Yuancai Xie

doi:10.21037/atm-21-3456

Circular RNA _0015278 inhibits the progression of non-small cell lung cancer through regulating the microRNA 1278/SOCS6 gene axis

Ann Transl Med. 2021 Aug;9(15):1255. doi: 10.21037/atm-21-3456.

Authors

Yiwang Ye¹, Xuan Wu², Feihu Long¹, Wei Yue¹, Da Wu¹, Yuancai Xie¹

Affiliations

¹ Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, China.
² Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, China.

Abstract

Background: Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. Deepening understanding of the pathogenesis of NSCLC is quite important for its treatment. Circular (circ) RNA_0015278 has been found to be downregulated in NSCLC, but its role in NSCLC and the underlying regulatory mechanism is unknown.

Methods: Circ_0015278, microRNA (miR)-1278 and SOCS6 were analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cell proliferation. The colony forming capacity and invasion of NSCLC cells were assessed with colony formation and transwell assays, respectively. The interaction among circ_0015278, miR-1278, and SOCS6 was evaluated using luciferase, receptor interacting protein (RIP), and RNA-pull down assays. Cell apoptosis was analyzed using flow cytometry. A subcutaneous NSCLC xenograft mouse model was established for evaluating circ_0015278-mediated effects on the growth of NSCLC in vivo.

Results: Circ_0015278 was downregulated in NSCLC tissues and cells, and its reduced expression indicated poor prognosis. Overexpression of circ_0015278 restrained the proliferation, colony formation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells and induced NSCLC cell apoptosis. Moreover, overexpression of circ_0015278 inhibited the growth of NSCLC in vivo. Mechanically, circ_0015278 acted as an miR-1278 sponge to reduce its quantity, and miR-1278 targeted SOCS6 to inhibit its expression in NSCLC cells. Circ_0015278 promoted SOCS6 expression by sponging miR-1,278 in NSCLC cells. Overexpression of circ_0015278 attenuated the malignant phenotypes of NSCLC through sponging miR-1278 and consequently promoting SOCS6 expression.

Conclusions: We demonstrated for the first time that circ_0015278 attenuated the progression of NSCLC via targeting the miR-1278/SOCS6 axis, which provides potential diagnostic biomarkers and therapeutic targets.

Keywords: Circular RNA_0015278; SOCS6; invasion; microRNA 1278; migration.