Non-small-cell lung cancer (NSCLC) is a major cause for cancer-related deaths around the globe, partially due to the frequent recurrence and metastasis. Leucine-rich-alpha2-glycoprotein 1 (LRG1) is reportedly upregulated in several cancers including NSCLC; however, its functions in NSCLC remain elusive. We used quantitative real-time PCR and western blot assays to evaluate the expression patterns of LRG1 in tumor tissues collected from NSCLC patients, as well as NSCLC cell lines, and examined the effects of LRG1 on the proliferation, migration, and invasion of NSCLC cells. Further, we isolated exosomes from the blood of NSCLC patients, as well as NSCLC cell cultures, and assessed the impact of exosome exposure on the angiogenic capacities of human umbilical vein endothelial cells. LRG1 was upregulated in NSCLC tissues and cells and induced an enhancement of NSCLC cell proliferation, migration, and invasion. In addition, LRG1 was enriched in the exosomes derived from NSCLC tissue and cells, and mediated a proangiogenic effect via the activation of transforming growth factor β (TGF-β) pathway. Exosomal LRG1 derived from NSCLC cells promotes angiogenesis via TGF-β signaling and possesses the potential of a therapeutic target in NSCLC treatment.

BackgroundImmunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity.MethodsThe expression of MACC1, c‐Met, and PDL1 in human GC tissues was first assessed using quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c‐Met, and PDL1 using RT‐PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo.ResultsWe found that expression of MACC1, c‐Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c‐Met and PDL1 expression levels, and c‐Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo.ConclusionsFrom these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.

Exosomes, released from various cell types, serve as vehicles of intercellular communication. Rearranged anaplastic lymphoma kinase (ALK) has been detected in exosomes released from cancer cells in ALK-positive nonsmall cell lung cancer (NSCLC), however, the functional consequence of ALK in exosomes has not been studied. This study aims to address whether exosomal ALK release is affected by stress, and whether exosomal ALK can modulate survival of recipient cells in vitro and in vivo. Exosomes, isolated from ALK-containing H3122 cells with (Exo-Apo) or without (Exo-Ctrl) irradiation treatment, were transferred to recipient H3122 cells in vitro or mouse xenograft in vivo. Western blot, flow cytometry, MTT, and xenograft were employed to respectively assess activation of the ALK pathway, apoptosis, cell viability, and tumor growth. Exo-Apo contained much higher levels of phosphorylated ALK (p-ALK) than that of Exo-Ctrl, and it activated AKT, STAT3, and the ERK pathway in recipient H3122 cells. ALK-specific inhibitors, including Crizotinib, Ceritinib, and TAE684, exhibited less effects on H3122 cells preincubated with Exo-Apo than on those treated with Exo-Ctrl in either inhibition of cell viability or promotion of apoptosis. Moreover, in an H3122 xenograft model, the Exo-Apo treatment resulted in a greater tumor growth and less sensitivity to Ceritinib than the Exo-Ctrl treatment. The ALK protein cargo in exosomes could be a key element to drive tumor growth and compromise therapeutic efficacy of ALK inhibitors for ALK-positive NSCLC.

Objective. In order to investigate the effect of lncRNA FOXD2-AS1 on breast cancer cells proliferation, migration, and drug resistance as well as its molecular mechanism. Methods. Real-time PCR was used to detect the expression of breast cancer tissues and cells from patients admitted to our hospital and the expression of lncRNA FOXD2-AS1 in MCF-7/ADR in adriamycin- (ADR-) resistant breast cancer cells. After interfering with or overexpressing lncRNA FOXD2-AS1 in MCF-7/ADR cells, cell proliferation, apoptosis, invasion, and migration were detected using CCK-8, flow cytometry, Transwell assay, and scratch test, respectively. The protein levels of PI3K, p-PI3K, AKT, and p-AKT in the PI3K/AKT signaling pathway were detected by Western blot. Results. lncRNA FOXD2-AS1 was upregulated in breast cancer tissues and cells and increased cell drug resistance to ADR. Downregulation of lncRNA FOXD2-AS1 inhibited invasion and migration of MCF-7/ADR cells, promoted apoptosis, increased chemosensitivity of MCF-7/ADR cells, and inhibited the activity of PI3K/AKT signaling pathway in MCF-7/ADR cells. Conclusions. lncRNA FOXD2-AS1 can promote the proliferation, invasion, migration, and drug resistance of breast cancer cells, inhibit apoptosis, and accelerate the development of breast cancer by positively regulating the PI3K/AKT signaling pathway.

OBJECTIVE: Recent studies suggest that abnormal snoRNA expression may play crucial role in tumor development and progression. In the study, we aim to explore the clinical significance and functional role of Small nucleolar RNA 78 (SNORD78) in breast cancer.PATIENTS AND METHODS: The expression of SNORD78 in 92 breast cancer and adjacent non tumor tissues was analyzed by quantitative real time polymerase chain reaction (qRT-PCR). The association between SNORD78 expression and clinicopathological factors was evaluated. The biological functions in vitro were examined by MTT cell proliferation, colony formation and transwell invasion assays. QRT-PCR and Western blot assays were used to analyze the mRNA and protein expression of WNT1, GSK3β and β-catenin.RESULTS: SNORD78 expression showed a significant increase in breast cancer tissues and cell lines. Higher SNORD78 expression positively was related to lymph node metastasis and TNM stage in patients. Furthermore, knockdown of SNORD78 inhibited the abilities of cell proliferation, colony formation, and cell invasion in MDA-MB-231 and SKBR-3 cells. Moreover, we demonstrated that knockdown of SNORD78 inhibited WNT/β-catenin signaling pathway in MDA-MB-231 and SKBR-3 cells via downregulating the relative protein expression of WNT1 and β-catenin and upregulating the GSK3β expression.CONCLUSION: Our results indicated that SNORD78 may be potential therapeutic target for breast cancer.