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LncRNA OGFRP1 promotes cell proliferation and suppresses cell radiosensitivity in gastric cancer by targeting the miR-149-5p/MAP3K3 axis
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2022-01-20 , DOI: 10.1007/s10735-022-10058-w
Huihao Qin 1 , Xing Li 1 , Wei Zhang 1 , Zhiqiang Ding 1
Affiliation  

Gastric cancer (GC) is an aggressive malignancy with high incidence and mortality. Radiotherapy is a common treatment for patients with advanced GC. Many long noncoding RNAs (lncRNAs) have been verified to affect the radiosensitivity of multiple cancers in previous studies. Nevertheless, whether lncRNA opioid growth factor receptor pseudogene 1 (OGFRP1) affects the radiosensitivity of GC has not been determined. We hypothesized that OGFRP1 might affect cellular processes in GC development. The present study aims to explore the role of OGFRP1 in GC development. First, high expression of OGFRP1 in GC tissues and cells was determined through RT-qPCR. Subsequently, functional assays including colony formation assays, 5-Ethynyl-2′-deoxyuridine assays and flow cytometry analyses were performed to probe the biological functions of OGFRP1 in GC. Specifically, the effect of OGFRP1 on the radiosensitivity of GC cells was detected. Subsequently, with the help of the starBase tool, we found that miR-149-5p might bind to OGFRP1, which was confirmed through a luciferase reporter assay. Furthermore, we identified that MAP3K3 was targeted by miR-149-5p in GC cells. Finally, the results from rescue experiments validated that enhanced MAP3K3 expression counteracted the effect of OGFRP1 silencing on GC cell proliferation, apoptosis and radiosensitivity. Overall, OGFRP1 was determined to promote GC cell proliferation while suppressing cell apoptosis and radiosensitivity by regulating the miR-149-5p/MAP3K3 axis.



中文翻译:

LncRNA OGFRP1通过靶向miR-149-5p/MAP3K3轴促进胃癌细胞增殖并抑制细胞放射敏感性

胃癌(GC)是一种侵袭性恶性肿瘤,发病率和死亡率都很高。放疗是晚期 GC 患者的常见治疗方法。在先前的研究中,许多长链非编码 RNA (lncRNA) 已被证实会影响多种癌症的放射敏感性。然而,lncRNA阿片类生长因子受体假基因1(OGFRP1)是否影响GC的放射敏感性尚未确定。我们假设 OGFRP1 可能会影响 GC 发育中的细胞过程。本研究旨在探讨 OGFRP1 在 GC 发展中的作用。首先,通过 RT-qPCR 确定 OGFRP1 在 GC 组织和细胞中的高表达。随后,进行了功能测定,包括集落形成测定、5-Ethynyl-2'-脱氧尿苷测定和流式细胞术分析,以探测 OGFRP1 在 GC 中的生物学功能。具体来说,检测了OGFRP1对GC细胞放射敏感性的影响。随后,在 starBase 工具的帮助下,我们发现 miR-149-5p 可能与 OGFRP1 结合,这一点通过荧光素酶报告基因检测得到证实。此外,我们发现 MAP3K3 在 GC 细胞中被 miR-149-5p 靶向。最后,救援实验的结果证实,增强的 MAP3K3 表达抵消了 OGFRP1 沉默对 GC 细胞增殖、凋亡和放射敏感性的影响。总体而言,OGFRP1 被确定为通过调节 miR-149-5p/MAP3K3 轴来促进 GC 细胞增殖,同时抑制细胞凋亡和放射敏感性。这通过荧光素酶报告基因测定得到证实。此外,我们发现 MAP3K3 在 GC 细胞中被 miR-149-5p 靶向。最后,救援实验的结果证实,增强的 MAP3K3 表达抵消了 OGFRP1 沉默对 GC 细胞增殖、凋亡和放射敏感性的影响。总体而言,OGFRP1 被确定为通过调节 miR-149-5p/MAP3K3 轴来促进 GC 细胞增殖,同时抑制细胞凋亡和放射敏感性。这通过荧光素酶报告基因测定得到证实。此外,我们发现 MAP3K3 在 GC 细胞中被 miR-149-5p 靶向。最后,救援实验的结果证实,增强的 MAP3K3 表达抵消了 OGFRP1 沉默对 GC 细胞增殖、凋亡和放射敏感性的影响。总体而言,OGFRP1 被确定为通过调节 miR-149-5p/MAP3K3 轴来促进 GC 细胞增殖,同时抑制细胞凋亡和放射敏感性。

更新日期:2022-01-20
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