Glucose metabolism is a common target for cancer regulation and microRNAs (miRNAs) are important regulators of this process. Here we aim to investigate a tumor‐suppressing miRNA, miR‐33b, in regulating the glucose metabolism of non‐small cell lung cancer (NSCLC). In our study, quantitative real‐time polymerase chain reaction (qRT‐PCR) showed that miR‐33b was downregulated in NSCLC tissues and cell lines, which was correlated with increased cell proliferation and colony formation. Overexpression of miR‐33b through miR‐33b mimics transfection suppressed NSCLC proliferation, colony formation, and induced cell‐cycle arrest and apoptosis. Meanwhile, miR‐33b overexpression inhibited glucose metabolism in NSCLC cells. Luciferase reporter assay confirmed that miR‐33b directly binds to the 3′‐untranslated region of lactate dehydrogenase A (LDHA). qRT‐PCR and Western blot analysis showed that miR‐33b downregulated the expression of LDHA. Moreover, introducing LDHA mRNA into cells over‐expressing miR‐33b attenuated the inhibitory effect of miR‐33b on the growth and glucose metabolism in NSCLC cells. Taken together, these results confirm that miR‐33b is an anti‐oncogenic miRNA, which inhibits NSCLC cell growth by targeting LDHA through reprogramming glucose metabolism.
Introduction: LncRNA MIR503HG has been reported to participate in liver cancer and ALK-negative anaplastic large-cell lymphoma, while its role in non-small cell lung cancer (NSCLC) is unknown. We therefore investigated the functions of lncRNA MIR503HG in NSCLC. Methods: MIR503HG expression in paired cancer and non-cancer tissues from NSCLC patients was analyzed by RT-qPCR. The interaction between cyclin D1 and MIR503HG was analyzed by overexpression experiments. Cell cycle analysis was performed by flow cytometry. Cell proliferation was analyzed by CCK-8 assay. Results: MIR503HG was downregulated in NSCLC and low levels of MIR503HG were associated with poor survival. In contrast, cyclin D1 was upregulated in NSCLC, and cyclin D1 and MIR503HG were inversely correlated. In NSCLC cells, overexpression experiments revealed that MIR503HG functioned as an upstream inhibitor of cyclin D1. MIR503HG overexpression led to G1 cell cycle arrest, while overexpression of cyclin D1 attenuated the effects of MIR503HG overexpression. Similarly, MIR503HG overexpression resulted in reduced cell proliferation rate, while overexpression of cyclin D1 caused the increased cell proliferation rate and attenuated effects of MIR503HG overexpression. Conclusion: MIR503HG inhibits NSCLC cell proliferation by inducing cell cycle arrest through the downregulation of cyclin D1.
To evaluate the effectiveness of ginsenoside Rg3 alone or in combination with cyclophosphamide (CPA) on tumor growth and angiogenesis in human lung cancer, 54 female athymic mice were transplanted with lung cancer cells (A549) which then were randomly divided into 4 groups: Ginsenoside Rg3 group, CPA group, ginsenoside Rg3 plus CPA group and control group. Ginsenoside Rg3 of 3.0 mg/kg (once/day for 10 days) and CPA of 20.0 mg/kg (once/day for 10 days) were intraperitoneally given to mice for consecutive 10 days. Seven mice selected from each group were sacrificed 18 days later. The survival time of the remaining 7 mice in each group was recorded. The life elongation rate, proliferating cell nuclear antigen labeling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) in the tumor tissues were evaluated. The quality of life of mice with administration of ginsenoside Rg3 alone or ginsenoside Rg3 plus CPA were better with longer survival time, when compared with other groups. The PCNALI, MVD and VEGF expression in mice of the treated groups were significantly lowered when compared with that of the control group. Additionally, the MVD of mice in groups with treatment of ginsenoside Rg3 alone or ginsenoside Rg3 plus CPA were lower than that in the CPA group. Tumor growth and angiogenesis in lung cancer were profoundly inhibited by ginsenoside Rg3 alone or in combination with CPA. The synergistic anticancer effects of ginsenoside Rg3 and CPA improved the survival time in lung cancer.
Objective: Fat cells-derived extracellular vesicles (FC-EVs) play a role in regulating the tumor microenvironment in cancers by transporting RNAs. MicroRNAs (miRNAs) are vital regulators of cancer development. This study was conducted to explore the role of FC-EVs in the proliferation and migration of non-small cell lung cancer (NSCLC) cells, providing targets for NSCLC treatment. background: Fat cells-derived extracellular vesicles (FC-EVs) play a role in regulating the tumor microenvironment in cancers by transporting RNAs. Methods: The obese mouse model was established via high‐fat diet (HFD), followed by separation and characterization of FC-EVs (HFD-EVs). The levels of miR-99a-5p, precursor-miR-99a-5p, and heparan sulfate-glucosamine 3-sulfotransferase 3B1 (HS3ST3B1) were measured by RT-qPCR or Western blot assay. Cell proliferation and migration were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and wound healing assays. The expression of Cy3-labeled miR-99a-5p in A549 cells (one NSCLC cell line) was observed via confocal microscopy. The binding of miR-99a-5p to HS3ST3B1 was analyzed by the dual luciferase assay. Rescue experiments were performed to confirm the role of HS3ST3B1 in NSCLC cells. objective: This study was conducted to explore the role of FC-EVs in the proliferation and migration of non-small cell lung cancer (NSCLC) cells, providing targets for NSCLC treatment. Results: miR-99a-5p was upregulated in adipose tissues, FCs, and HFD-EVs. HFD-EVs mitigated the proliferation and migration of NSCLC cells. HFD-EVs transported miR-99a-5p into A549 cells, which upregulated miR-99a-5p expression and inhibited HS3ST3B1 expression in A549 cells. HS3ST3B1 overexpression reversed the inhibition of HFD-EVs on the proliferation and migration of NSCLC cells. method: The obese mouse model was established via high‐fat diet (HFD), followed by separation and characterization of FC-EVs (HFD-EVs). The levels of microRNA (miR)-99a-5p, precursor-miR-99a-5p, and heparan sulfate-glucosamine 3-sulfotransferase 3B1 (HS3ST3B1) were measured by RT-qPCR or Western blot assay. Cell proliferation and migration were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and wound healing assays. The expression of Cy3-labeled miR-99a-5p in A549 cells was observed via confocal microscopy. The binding of miR-99a-5p to HS3ST3B1 was analyzed by the dual luciferase assay. Rescue experiments were performed to confirm the role of HS3ST3B1 in NSCLC cells. Conclusion: HFD-EVs transported miR-99a-5p into NSCLC cells and inhibited HS3ST3B1, thereby inhibiting proliferation and migration of NSCLC cells. result: miR-99a-5p was upregulated in adipose tissues, FCs, and HFD-EVs. HFD-EVs mitigated the proliferation and migration of NSCLC cells. HFD-EVs transported miR-99a-5p into A549 cells, which upregulated miR-99a-5p expression and inhibited HS3ST3B1 expression in A549 cells. HS3ST3B1 overexpression reversed the inhibition of HFD-EVs on the proliferation and migration of NSCLC cells. conclusion: HFD-EVs transported miR-99a-5p into NSCLC cells and inhibited HS3ST3B1, thereby inhibiting proliferation and migration of NSCLC cells. other: None.
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