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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.

Abstract. The current study examined the role of Raf kinase inhibitor protein (RKIP) in non-small cell lung cancer (NSCLC) metastasis. A total of 100 patients with NSCLC were recruited following pathological diagnosis in the First Affiliated Hospital of Bengbu Medical College. The patients were classified and statistically analyzed according to their clinicopathological characteristics and tumor-node-metastasis stage. Paired tumor tissue and adjacent non-tumor tissue samples were subject to pathological diagnosis and western blot analysis. Transient transfection and lentivirus particle vector-mediated RKIP overexpression, small interfering RNA-mediated silencing, Transwell assays and immunocytochemistry methods were employed to elucidate the role and underlying mechanisms of RKIP and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in NSCLC metastasis. Furthermore, in order to examine the in vivo effects of RKIP, recombinant lentivirus particles containing the RKIP gene were administrated in a mouse NSCLC tumor model via tail vein injection. The results revealed reduced RKIP expression levels in NSCLC tissue compared with corresponding non-cancer tissue. Additionally, RKIP expression levels were inversely associated with NSCLC intra-lung, lymph node and long-distance metastasis. The results also indicated that RKIP was able to block STAT3 activation via phosphorylation and inhibit NSCLC-cell metastasis in vitro. Furthermore, RKIP knockdown was able to promote STAT3 phosphorylation and cell metastasis in NSCLC cell lines. During in vivo experiments, RKIP overexpression was able to suppress xenograft tumor metastasis in nude mice. Therefore, RKIP may be an important factor in cancer cell metastasis in patients with NSCLC, and RKIP may inhibit NSCLC-cell invasion by blocking the activation of the JAK/STAT3 signaling pathway. IntroductionLung cancer has increased in incidence in the developing world since 2008, from 1.8 to 2 million per year, and this trend is predicted to continue in the future (1). Non-small cell lung cancer (NSCLC) is among the most malignant types of cancer, and has a high mortality rate (2). Approximately 80-90% of lung cancer cases are of NSCLC, and 50-70% of these patients are diagnosed at the advanced stage of disease (1,3). The survival time of patients with lung cancer is 5 years in 10-15% of cases, with the remaining exhibiting poorer survival times (1). Therefore, the early prevention of NSCLC metastasis is a key factor in lung cancer prevention and the development of novel therapeutic agents. A number of studies have investigated the mechanisms underlying NSCLC metastasis (4,5); however, the exact mechanisms underlying this process require further elucidation.Raf kinase inhibitor protein (RKIP) is a small evolutionarily conserved protein, which was initially identified to function as a physiological inhibitor of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway (6). RKIP inhib...

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Iron metabolism has been shown to hand over cancer stem cell, which is regarded as the root of tumor progression, recurrence and chemoresistance. This study aims to explore whether iron metabolism is involved in etoposide-and cisplatin-induced stemness in small cell lung cancer (SCLC) cells. Here, analysis on tumor-sphere formation and stemness marker expression is performed to determine whether etoposide and cisplatin can induce SCLC cell stemness. Online dataset analysis is constructed to determine the correlation between iron transportation and the survival of lung cancer patients. Chromatin immunoprecipitation combined with rescuing experiments are carried out to reveal the underlying mechanisms. Additionally, the non-lethal doses of etoposide and cisplatin can induce SCLC cell stemness in a concentration-dependent manner and reduce the lysosome iron concentration dependent on Ferritin expression, which is positively regulated by HIF-1α/β. Moreover, HIF-1α/β can directly bind to Ferritin promoter region. This HIF/Ferritin axis is responsible for etoposide-and cisplatin-induced iron reduction in lysosomes and stemness of SCLC cells. This work demonstrates that iron in lysosomes is essential for etoposide and cisplatin-induced stemness of SCLC cells, which is regulated by the HIF/Ferritin axis.