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miRNA-1-FAM83A 轴功能障碍参与肺癌细胞的生长和迁移。

Involvement of MicroRNA-1-FAM83A Axis Dysfunction in the Growth and Motility of Lung Cancer Cells.

机构信息

Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.

Division of Chest Medicine, Department of Internal Medicine, CHENG HSIN General Hospital, Taipei 11221, Taiwan.

出版信息

Int J Mol Sci. 2020 Nov 22;21(22):8833. doi: 10.3390/ijms21228833.

Abstract

Lung cancer is the most prevalent types of cancer and the leading cause of cancer-related deaths worldwide. Among all cancers, lung cancer has the highest incidence, accompanied by a high mortality rate at the advanced stage. Favorable prognostic biomarkers can effectively increase the survival rate in lung cancer. Our results revealed (Family with sequence similarity 83, member A) overexpression in lung cancer tissues compared with adjacent normal tissues. Furthermore, high expression was closely associated with poor lung cancer survival. Here, through siRNA transfection, we effectively inhibited expression in the lung cancer cell lines H1355 and A549. FAM83A knockdown significantly suppressed the proliferation, migration, and invasion ability of these cells. Furthermore, knockdown could suppress Epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinase (MAPK)/Choline kinase alpha (CHKA) signaling activation in A549 and H1355. By using a bioinformatics approach, we found that overexpression in lung cancer may result from miR-1-3p downregulation. In summary, we identified a novel axis could partially modulate the EGFR/choline phospholipid metabolism signaling pathway, which suppressed lung cancer growth and motility. Our findings provide new insights for the development of lung cancer therapeutics.

摘要

肺癌是最常见的癌症类型,也是全球癌症相关死亡的主要原因。在所有癌症中,肺癌的发病率最高,晚期死亡率也很高。有利的预后生物标志物可以有效地提高肺癌患者的生存率。我们的研究结果表明,家族与序列相似性 83,成员 A(Family with sequence similarity 83, member A)在肺癌组织中的表达高于相邻正常组织。此外,高表达与肺癌患者的不良预后密切相关。在这里,我们通过 siRNA 转染,有效地抑制了肺癌细胞系 H1355 和 A549 中的表达。FAM83A 的敲低显著抑制了这些细胞的增殖、迁移和侵袭能力。此外,FAM83A 的敲低可以抑制 A549 和 H1355 中表皮生长因子受体(Epidermal growth factor receptor,EGFR)/丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)/胆碱激酶 α(Choline kinase alpha,CHKA)信号的激活。通过生物信息学方法,我们发现肺癌中 FAM83A 的过表达可能是由于 miR-1-3p 的下调。总之,我们发现了一个新的 FAM83A/miR-1-3p/EGFR 轴,该轴可以部分调节 EGFR/胆碱磷脂代谢信号通路,抑制肺癌的生长和迁移。我们的研究结果为肺癌治疗的发展提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac66/7700477/70a5f9be92bd/ijms-21-08833-g001.jpg

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