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TMEM119 通过 PDGFRB/PI3K/AKT 信号通路促进卵巢癌细胞的增殖、侵袭和迁移。

TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, China.

Department of Urology, First Hospital of China Medical University, Shenyang, China.

出版信息

J Transl Med. 2021 Mar 17;19(1):111. doi: 10.1186/s12967-021-02781-x.

Abstract

BACKGROUND

Ovarian cancer (OV) is the deadliest gynecological cancer. Transmembrane protein 119 (TMEM119) has been reported as oncogene in several human cancers. However, the function of TMEM119 in OV is still poorly known.

METHODS

Western blot and qRT-PCR were used to analyze TMEM119 levels. Transwell assays, wound healing assays, CCK-8 assays and EdU cell proliferation assays were designed to explore the function and potential mechanism of TMEM119 in malignant biological behaviors in OV.

RESULTS

TMEM119 was observed to be overexpressed in OV tissues and associated with poor survival in OV patients. Knockdown and overexpression experiments demonstrated that TMEM119 promoted proliferation, invasion, and migration in OV cells in vitro. TMEM119 mRNA expression was related to the pathways of focal adhesion according to Gene Set Enrichment Analyses and was correlated with the mRNA expression level of platelet-derived growth factor receptor beta (PDGFRB). TMEM119 exerted oncogenic effects partially by regulating the expression of PDGFRB and by activating the PI3K/AKT signaling pathway.

CONCLUSIONS

Collectively, our findings highlight the potential role of TMEM119 in the malignant biological behavior of OV, which may serve as a potential biomarker and a therapeutic candidate for OV.

摘要

背景

卵巢癌(OV)是致死率最高的妇科癌症。跨膜蛋白 119(TMEM119)已被报道为多种人类癌症的癌基因。然而,TMEM119 在 OV 中的功能仍知之甚少。

方法

使用 Western blot 和 qRT-PCR 分析 TMEM119 水平。设计 Transwell 测定、划痕愈合测定、CCK-8 测定和 EdU 细胞增殖测定,以探索 TMEM119 在 OV 恶性生物学行为中的功能和潜在机制。

结果

TMEM119 在 OV 组织中表达上调,与 OV 患者的不良生存相关。敲低和过表达实验表明,TMEM119 在体外促进 OV 细胞的增殖、侵袭和迁移。根据基因集富集分析,TMEM119 mRNA 表达与粘着斑途径有关,与血小板衍生生长因子受体β(PDGFRB)的 mRNA 表达水平相关。TMEM119 通过调节 PDGFRB 的表达并激活 PI3K/AKT 信号通路发挥致癌作用。

结论

总之,我们的研究结果强调了 TMEM119 在 OV 恶性生物学行为中的潜在作用,它可能成为 OV 的一个潜在的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad6/7968362/d936aa825d61/12967_2021_2781_Fig1_HTML.jpg

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