Circular RNA circ_0001287 inhibits the proliferation, metastasis, and radiosensitivity of non-small cell lung cancer cells by sponging microRNA miR-21 and up-regulating phosphatase and tensin homolog expression.

As a type of non-coding RNA, circular RNA (circRNA) figures prominently in human cancer progression. Nonetheless, the expression, function, and regulatory mechanism of circ_0001287 in non-small cell lung cancer (NSCLC) remain obscure. In this work, quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to quantify circ_0001287 and miR-21 expressions in NSCLC tissues and cells. The relationship between circ_0001287 expression and the clinicopathological parameters of NSCLC patients was examined. Cell counting kit-8 (CCK-8), 5-bromo-2©-deoxyuridine (BrdU), and Transwell experiments were conducted to detect the multiplication, migration, and invasion of NSCLC cells after circ_0001287 was overexpressed or knocked down. The survival of NSCLC cells was studied using colony formation experiment under different doses of radiation. RNA immunoprecipitation (RIP) experiment and luciferase reporter gene experiment verified the binding relationship between circ_0001287 and miR-21. Western blot was employed to examine the regulatory effects of circ_0001287 and miR-21 on phosphatase and tensin homolog (PTEN) expression. We reported that circ_0001287 expression was down-modulated in NSCLC tissues and cell lines. Besides, circ_0001287 low expression was associated with low differentiation and positive lymph node invasion of NSCLC. Circ_0001287 overexpression suppressed the multiplication, migration, invasion, and radioresistance of NSCLC cells, whereas circ_0001287 knockdown promoted the above phenotypes. Circ_0001287 could adsorb miR-21 and repress its expression, and indirectly up-modulate PTEN expression in NSCLC cells. Taken together, circ_0001287/miR-21/PTEN axis is probably involved in regulating NSCLC cell multiplication, metastasis, and radioresistance.

Overexpression of microRNA-124-5p sensitizes non-small cell lung cancer cells to treatment with 5-fluorouracil via AEG-1 regulation.

Chemotherapeutic resistance represents a major obstacle for the treatment of patients with non-small cell lung cancer (NSCLC); however, the associated molecular mechanisms underpinning the development of resistance remain poorly characterized. In the current study, 5-fluorouracil (5-FU)-resistant A549 cells (A549/5-FU) were generated from A549 cells. Reverse transcription-quantitative PCR and western blotting were used to detect microRNA(miR)-124-5p and astrocyte elevated gene 1 (AEG-1) expression levels in cells and tumor tissues. In addition, the cytotoxic effect of 5-FU on the cells was determined using the Cell Counting Kit-8 assay, and the Dual-luciferase reporter assay was used to validate AEG-1 as a target gene of miR-124-5p. Transfection with a miR-124-5p mimic enhanced inhibition of cell viability induced by 5-FU in A549/5-FU cells, whereas miR-124-5p inhibitor transfection partially reversed 5-FU-induced cell viability inhibition in A549 and H1299 cells. A decrease in miR-124-5p expression level was observed in A549/5-FU cells compared with the parental A549 cells. Furthermore, AEG-1 was predicted as a target gene of miR-124-5p, and its expression was increased in A549/5-FU cells compared with A549 cells. Additionally, the upregulation of miR-124-5p was associated with lower expression levels of AEG-1 in A549/5-FU cells, compared with parental A549 cells. Moreover, the Dual-luciferase reporter assay confirmed the ability of miR-124-5p to bind directly to the 3'-untranslated region of AEG-1 mRNA. Notably, the overexpression of AEG-1 reversed the ability of the miR-124-5p mimic to increase the sensitivity of A549/5-FU cells to 5-FU treatment. Additionally, a significant negative correlation between miR-124-5p expression and AEG-1 mRNA levels was detected in 40 pairs of NSCLC tissues and their corresponding adjacent paracancerous tissues. The results of the present study indicated that miR-124-5p may regulate the chemotherapeutic sensitivity of NSCLC cells, and may therefore represent a promising biomarker or therapeutic target for patients with NSCLC.