Yiqian Liu, Ling Zhang, Jian Wang, Jiali Xu, Jing Xu, Mengyan Xie, Rong Wang
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引用次数: 0
Abstract
Abnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Transmission electron microscopy and nanoparticle tracking analysis were conducted to verify NSCLC cell-derived small extracellular vesicles (sEVs). MicroRNA (miRNA/miR) and mRNA expression levels were determined using reverse transcription-quantitative PCR, while protein expression levels were determined using western blot analysis and immunofluorescence. In addition, potential binding sites between miR-326 and SNHG12/SLC7A11 were verified using a dual-luciferase reporter assay. Cell behavior was detected using flow cytometry, colony formation, wound healing and Transwell assays, and xenograft experiments were conducted to confirm the roles of SNHG12 in NSCLC. H&E staining was used for histological analysis, and each experiment was repeated three times. Results of the present study demonstrated that NSCLC-derived SNHG12 promoted type-2 tumor-associated macrophage (TAM2) polarization. However, the decrease of SNHG12 expression in EVs reduced TAM2 polarization, weakened NSCLC cell proliferation, migration and invasion, and promoted tumor cell ferroptosis. Moreover, results of the present study revealed that SNHG12 knockdown markedly suppressed tumor growth and the metastasis of NSCLC. In addition, SNHG12 upregulated SLC7A11 expression via binding to miR-326. Overexpressed SLC7A11 promoted tumor aggressiveness and suppressed the ferroptosis of NSCLC cells. Collectively, results of the present study revealed that SNHG12 suppressed ferroptosis and promoted the metastasis of NSCLC, further demonstrating that high SNHG12 expression levels may be indicative of poor clinical outcomes for patients with NSCLC. Thus, the present study highlighted that the SNHG12/miR-326/SLC7A11 axis may exhibit potential as a novel target for the treatment of NSCLC.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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