Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR‑145 was reported to occur in various types of human cancer; however, the role of miR‑145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR‑145 on metastasis and epithelial‑mesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR‑145 regulates EMT were examined. The miR‑145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR‑145 regulates EMT, a luciferase reporter assay was performed to determine whether miR‑145 targeted Oct4. In addition, the expression of Wnt3a and β‑catenin in A549 cells was measured following transfection with small hairpin RNA‑Oct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR‑145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/β‑catenin signaling pathway.

Abstract. Non-small cell lung cancer (NSCLC) accounts for >80% of all cases of lung cancer and can be divided into lung adenocarcinoma (LAC), large-cell carcinoma (LCC), and squamous cell carcinoma (SCC). Accumulating evidence suggests that MTSS1, which is a newly discovered protein associated with tumor progression and metastasis, may have differential roles in cancer malignancy. As it has been demonstrated that MTSS1 is overexpressed in NSCLC and may be an independent prognostic factor in patients with SCC, the present study explored the differential roles of MTSS1 in the invasion and proliferation of different subtypes of NSCLC. Stable overexpression and knockdown of MTSS1 was performed in human NSCLC H920 (LAC), H1581 (LCC) and SW900 cell lines (SCC), and western blot, cell invasion, proliferation and FAK activity analyses were used to investigate the effects. Overexpression of MTSS1 enhanced the invasion and proliferation abilities of H920 and H1581 cells, and these effects were abolished by treatment with selective FAK inhibitor 14, which did not affect the expression of MTSS1. Notably, overexpression of MTSS1 inhibited invasion and proliferation in SW900 cells, and this effect was enhanced by the selective FAK inhibitor. Knockdown of MTSS1 decreased the invasion and proliferation abilities of H920 and H1581 cells, whereas knockdown increased invasion and proliferation in SW900 cells. Furthermore, while overexpression of MTSS1 induced FAK phosphorylation and activity in H920 and H1581 cells, MTSS1 overexpression inhibited FAK phosphorylation/activity in SW900 cells. Knockdown of MTSS1 decreased FAK phosphorylation/activity in H920 and H1581 cells, whereas knockdown increased these processes in SW900 cells. To the best of our knowledge, the present study was the first to demonstrate that MTSS1 has differential roles in various subtypes of NSCLC, acting via a FAK-dependent mechanism. The results indicated that MTSS1 may enhance invasion and proliferation in LAC and LCC cells, whereas MTS11 inhibits these processes in SCC cells. These findings provide novel insight into the functional role of MTSS1 in cancer and may help elucidate therapeutic strategies for the treatment of various types of cancer. IntroductionLung cancer remains the leading cause of death from cancer worldwide, with ~1.4 million deaths each year (1). Non-small cell lung cancer (NSCLC), which is the predominant form of the disease, accounts for >80% of all cases of lung cancer (2). There are three types of NSCLC: Lung adenocarcinoma (LAC), large-cell carcinoma (LCC) and squamous cell carcinoma (SCC) (3). Despite great advances in surgery, chemotherapy and radiotherapy, the long-term survival of patients with NSCLC remains poor due to rapid growth and high rate of recurrence and metastasis (4,5). Therefore, it is imperative that the precise molecular mechanisms underlying the invasion and metastasis of NSCLC are investigated.Metastasis suppressor 1 (MTSS1), which is also known as MIM (missing-in-metastasis), was first identified as a potential...

Abstract. Clinical studies have reported evidence for the involvement of octamer-binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial-mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β-catenin/E-cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β-catenin/E-cadherin complex degradation and regulating nuclear localization of β-catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β-catenin/E-cadherin complex was regulated by Oct4 during the process of EMT. IntroductionLung cancer is one of the most prevalent types of malignant tumor worldwide, with a five-year survival rate of ~16% (1). Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Therefore, it is necessary to elucidate the molecular mechanisms of lung cancer metastasis in order to develop effective treatment options.Epithelial-mesenchymal transition (EMT) is a process characterized by downregulation of epithelial markers and upregulation of mesenchymal markers (2,3). Previous studies have proposed that EMT may be a key step in the progression of tumor cell metastasis (4-6).Octamer-binding protein 4 (Oct4), a transcription factor that belongs to the Pit-Oct-Unc (POU) family, has been reported to be a master regulator of maintenance and differentiation in pluripotent cells. It has been suggested that Oct4 may be a key component of the regulation of self-renewal and differentiation in stem cells (7-9); in addition, Oct4 may also have a crucial role in cancer development (10). Chen et al (11) demonstrated that Oct4 expression was involved in the tumorigenesis and malignancy of lung cancer. The aims of the present study were to investigate the effect of Oct4 on the cell biology of lung cancer cells in vitro, elucidate the underlying mechanisms associated with lung cancer metastasis and examine the effect of Oct4 on the degradation of the β-catenin/E-cadherin complex degradation, a process strongly associated with EMT. Materials and methods Cell