Background Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA – circPTPRA– in NSCLC and characterized its molecular mechanism of action. Methods circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domain-containing protein 8 (RASSF8). Findings circPTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circPTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circPTPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression. Interpretation circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. Fund The Key research and development projects of Anhui Province (201904a0720079), the Natural Science Foundation of Anhui Province (1908085MH240), the Graduate Innovation Program of Bengbu Medical College (Byycx1843), the National Natural Science Foundation of Tibet (XZ2017ZR-ZY033) and the Science and Technology Project of Shannan (SNKJYFJF2017-3) and Academic Subsidy Project for Top Talents in Universities of Anhui in 2019 (gxbjZD16)

Background: Survivin is a structurally and functionally unique member of the inhibitor of apoptosis protein (IAP) family. It plays an important role, not only in regulating mitosis but also in inhibiting apoptosis. The current literature contains few reports on the transcriptional regulation of survivin expression in lung cancer.

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SummaryLong non-coding RNAs (lncRNAs) are increasingly recognized as important regulators in tumor development. This study aims to investigate the potential role oflncRNALEF1-AS1, in the progression of lung cancer. Quantitative real-time PCR (qRT-PCR) and western blot assays showed that LEF1-AS1 was upregulated while miR-544a was downregulated in lung cancer specimens and cells. Overexpression of LEF1-AS1 led to the enhancement of cell proliferation and invasion, revealed by CCK-8 assay and transwell assay. A negative correlation was found between LEF1-AS1 and miR-544a. BLAST analysis and dual-luciferase assay confirmed that FOXP1 is a downstream effector of miR-544a. Therefore, the LEF1-AS1/miR-544a/FOXP1 axis is an important contributor to lung cancer progression. Collectively, our novel data uncovers a new mechanism that governs tumor progression in lung cancer and provides new targets that may be used for disease monitoring and therapeutic intervention of lung cancer.

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