Background miR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy. Methods The expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p. Results miR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways. Conclusion miR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

中文翻译：

---

miR-100-3p通过靶向BMPR2抑制人胃癌细胞增殖并诱导细胞凋亡。

背景 据报道，miR-100 与胃癌 (GC) 的发生和进展密切相关。然而，miR-100-3p 在 GC 中的潜在机制仍不清楚。在这项研究中，我们打算研究 miR-100-3p 如何调节 GC 恶性肿瘤。方法通过定量实时PCR（qRT-PCR）检测miR-100-3p在体外（GES-1和GC细胞系）和体内（癌性和正常胃组织）的表达水平。MTT 和 PE/Annexin V 分析负责测量 miR-100-3p 对 GC 细胞增殖和凋亡的影响。使用有或没有基质胶的 Transwell 测定来检查 GC 细胞中的迁移和侵袭能力。通过转录组学分析和荧光素酶报告基因分析证实了 miR-100-3p 与骨形态发生蛋白受体 2 (BMPR2) 的相互作用。应用 qRT-PCR 和蛋白质印迹分析来确定 ERK/AKT 和 Bax/Bcl2/Caspase3 的表达，它们是导致 miR-100-3p 功能障碍的原因。结果miR-100-3p在GC细胞系和癌组织中表达下调，与BMPR2呈负相关。miR-100-3p 的缺失促进了肿瘤的生长和 BMPR2 的表达。一致地，miR-100-3p抑制对GC细胞的影响被BMPR2的敲低部分中和。miR-100-3p 的过表达同时抑制肿瘤生长并下调 BMPR2 表达。一致地，BMPR2的过表达部分中和了miR-100-3p过表达的影响。进一步研究表明，BMPR2介导了miR-100-3p下游的作用，可能间接调节ERK/AKT和Bax/Bcl2/Caspase3信号通路。结论 miR-100-3p作为肿瘤抑制miRNA，下调BMPR2，从而抑制ERK/AKT信号，激活Bax/Bcl2/Caspase3信号。这一发现为 GC 提供了新的见解，并有助于确定新的诊断和治疗靶点。