MiR-26a-5p Serves as an Oncogenic MicroRNA in Non-Small Cell Lung Cancer by Targeting FAF1.

PURPOSE: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers, with the FAS-associated factor 1 (FAF1) acting as a tumor suppressor. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we aimed to reveal the influence of miR-26a-5p on the regulation of FAF1 expression and NSCLC progression, with the motivation of identifying a potential therapeutic target for NSCLC treatment. METHODS: A dual-luciferase reporter assay was used to check for the direct targeting of FAF1 by miR-26a-3p. The miR-26a-5p inhibitor or FAF1 shRNA plasmid was transfected into A549 and H1299 cells to modulate FAF1 expression. Then, the effect of miR-26a-5p/FAF1 on cellular functions was investigated. MTT assay was used to evaluate cell viability. EdU proliferation assay and cell cycle assay were performed to analyze the effect of miR-26a-5p on cell replication and cell cycle. We used annexin V-FITC and PI to stain apoptotic cells, followed by flow cytometric analysis. Transwell and wound healing assays were performed to investigate metastasis. Moreover, the effect of miR-26a-5p/FAF1 on cancer progression was examined in vivo. Lastly, the underlying mechanism was uncovered using RT-qPCR, Western blotting, and TOP/FOP flash assay. RESULTS: miR-26a-5p was found to directly target FAF1 and downregulate its expression. Blocking miR-26a-5p inhibited the cell growth, migration, and invasion, but promoted cell apoptosis. In addition, this inhibited the growth of tumor in mice. FAF1 knockdown reversed the functions of miR-26a-5p. Further, miR-26a-5p/FAF1 was observed to play an important role in the Wnt signaling pathway, regulating the expression of genes such as AXIN, c-Myc, and cyclin-D1. CONCLUSION: Taken together, we show that miR-26a-5p functions as an oncogenic microRNA in NSCLC by targeting FAF1 and may serve as a potential target for NSCLC treatment.

MiR-504 inhibits cell proliferation and invasion by targeting LOXL2 in non small cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in tumor initiation and development. The aim of the study was to explore the clinicopathological role and functional effects of miR-504 in non small cell lung cancer (NSCLC). METHODS: Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was applied to detect the expression of miR-504 in 55 cases of NSCLC tissues and matched adjacent normal tissues in NSCLC patients. MTT, colony formation and transwell invasion assays were performed to evaluate the effects of miR-504 on cell proliferation and invasion, respectively. Dual luciferase reporter assay was used to verify that LOXL2 was a direct target of miR-504. QRT-PCR and western blot analysis were performed to analyze mRNA and protein expression. RESULTS: In the study, we demonstrated that miR-504 was notably downregulated in NSCLC tissues compared with adjacent normal tissues. Lower miR-504 expression positively correlated with lymph node metastasis and advanced TNM stage in patients. Furthermore, upregulation of miR-504 significantly inhibited cell proliferation, cell invasion and EMT process of NSCLC. QRT-PCR, western blot and luciferase reporter assays confirmed that miR-504 could bind to LOXL2 3'UTR region and regulate its expression. Moreover, ectopic expression of LOXL2 could rescue the inhibiting effects on cell proliferation and invasion induced by miR-504 in NSCLC cells. CONCLUSIONS: Our results indicated that miR-504 functioned as a tumor suppressor in NSCLC and may serve as a target of NSCLC treatment.

Novel diagnosis and treatment of esophageal granular cell tumor: report of 14 cases and review of the literature.

BACKGROUND: Granular cell tumors (GCT), especially in the esophagus, are rare neoplasms originating from the nervous system. There is still some controversy regarding the diagnosis and treatment of esophageal GCT. METHODS: We report 14 cases of esophageal GCT diagnosed and treated from January 2004 to March 2013. Their clinical manifestations, endoscopic image, endoscopic ultrasonography (EUS) appearance, pathology, immunohistochemistry, treatment, and prognosis were reviewed. RESULTS: The typical images of EUS were hypoechoic, homogenous, and smooth-edged tumors restricted to deep mucosal and submucosal layers. However, there were 2 cases with tumors invading muscular layer. Endoscopic ultrasonography was valuable to assess the tumor size, location, depth of invasion, and nature. According to EUS manifestation, 11 cases with lesions 3 cm or less in diameter without muscular layer invasion underwent endoscopic resection without complication and the other 3 cases underwent surgical resection. A new technique of submucosal tunnel endoscopic resection was performed in 3 submucosal cases with lesions ranging from 2 cm to 3 cm in diameter. All of these cases were benign and histology was necessary for differential diagnosis. CONCLUSIONS: Endoscopic ultrasonography plays an important guiding role in the diagnosis and treatment of esophageal GCT. Submucosal tunnel endoscopic resection is safe and effective. Further study is needed to determine whether this technique can be expanded into other applications.