Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR-21-5p/TXNIP axis.

BACKGROUND

Lung cancer is one of the most common malignancies globally and a significant component of cancer-related deaths. The lack of early diagnosis accounts for detecting approximately 75% of cancer patients at an intermediate to an advanced stage, with a low 5-year survival rate. Therefore, a more comprehensive understanding of the molecular mechanisms of lung cancer development is necessary to find reliable and effective therapeutic and diagnostic biomarkers.

METHODS

circ_SAR1A, miR-21-5p, and TXNIP in lung cancer tissues, animal xenografts, and cell lines were validated by qRT-PCR and western blotting analyses. RNase R digestion and nuclear/cytoplasm fractionation experiments were utilized to determine the stability and localization of circ_SAR1A in lung cancer cells. The binding between miR-21-5p and circ_SAR1A or TXNIP was confirmed by luciferase reporter, RNA pull-down, Spearman's correlation, and rescue assays. CCK-8, colony formation, flow cytometry, Transwell, and western blotting were utilized to illustrate the malignant behavior of lung cancer cells.

RESULTS

circ_SAR1A and TXNIP were down-regulated while miR-21-5p was up-regulated in lung cancer samples and cells. circ_SAR1A was located predominantly in the cytoplasm; it inhibited lung cancer growth in vitro and in vivo by sponging to miR-21-5p. miR-21-5p silencing suppressed lung cancer malignancy by targeting TXNIP.

CONCLUSIONS

circ_SAR1A is a critical negative regulator of lung carcinogenesis. circ_SAR1A/miR-21-5p/TXNIP attenuation inhibited lung cancer progression, presenting an ideal diagnostic and a potential therapeutic target.