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首页> 外文期刊>Journal of cellular physiology. >LncRNA HEIH/miR-939-5p interplay modulates triple-negative breast cancer progression through NOS2-induced nitric oxide production
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LncRNA HEIH/miR-939-5p interplay modulates triple-negative breast cancer progression through NOS2-induced nitric oxide production

机译:LncRNA HEIH / mir - 939 - 5 - p相互作用调节三阴性乳腺癌的进展NOS2-induced一氧化氮产量

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摘要

This study aimed to unravel the regulatory role of noncoding RNAs (ncRNA) on the nitric oxide (NO) machinery system in triple-negative breast cancer (TNBC) patients and to further assess the influence of NO-modulating ncRNAs on TNBC progression, immunogenic profile, and the tumor microenvironment (TME). The results revealed miR-939-5p and lncRNA HEIH as novel ncRNAs modulating NO machinery in TNBC. MiR-939-5p, an underexpressed microRNA (miRNA) in BC patients, showed an inhibitory effect on NOS2 and NOS3 transcript levels on TNBC cells. In contrast, HEIH was found to be markedly upregulated in TNBC patients and showed a modulatory role on miR-939-5p/NOS2/NO axis. Functionally, miR-939-5p was characterized as a tumor suppressor miRNA while HEIH was categorized as a novel oncogenic lncRNA in TNBC. Finally, knocking down of HEIH resulted in improvement of immunogenic profile of TNBC cells through inducing MICA/B and suppressing the immune checkpoint inhibitor PDL1. In the same context, knockdown of HEIH resulted in the alleviation of the immune-suppressive TME by repressing interleukin-10 and tumor necrosis factor-alpha levels. In conclusion, this study identifies miR-939-5p as a tumor suppressor miRNA while HEIH as an oncogenic lncRNA exhibiting its effect through miR-939-5p/NOS2/NO axis. Therefore, repressing BC hallmarks, improving TNBC immunogenic profile, and trimming TME.
机译:本研究旨在解决监管的作用非编码rna (ncRNA)一氧化氮(NO)机械系统三阴性乳腺癌(TNBC)患者和进一步评估对TNBC的影响NO-modulating ncRNAs发展、免疫原性剖面和肿瘤微环境(时差)。美国miR-939-5p和lncRNA HEIH ncRNAs小说调制在TNBC没有机械。公元前underexpressed microRNA (microRNA)患者,NOS2和NOS3有抑制作用对TNBC细胞转录水平。在TNBC HEIH被发现显著调节病人和调节作用mir - 939 - 5 - p / NOS2 /不轴。作为一个肿瘤抑制microrna的特点是当HEIH归类为小说致癌lncRNA TNBC。导致改善免疫原性的通过诱导云母/ B和TNBC细胞抑制免疫抑制剂PDL1检查站。在相同的情况下,降价HEIH造成的减轻immune-suppressive碰头通过抑制白细胞介素- 10”和肿瘤坏死因子-α水平。标识mir - 939 - 5 - p作为肿瘤抑制microrna虽然HEIH致癌lncRNA展示它影响通过mir - 939 - 5 - p / NOS2 /不轴。因此,压抑BC特征,改善TNBC免疫原性剖面和调整时间。

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