Chen Bing, Zheng Shiya, Jiang Feng
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital, Nanjing, China.
Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.
PeerJ. 2021 Sep 16;9:e12140. doi: 10.7717/peerj.12140. eCollection 2021.
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified.
miR-1293 expression and its association with LUAD patients' clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model.
We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients' pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression .
miR-1293 promoted the proliferation, migration and invasion of LUAD cells targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.
肺腺癌（LUAD）是肺癌最常见的组织学亚型。研究发现，miR-1293与LUAD患者的生存相关。遗憾的是，其在LUAD中的作用仍未完全阐明。
在TCGA数据库中分析miR-1293的表达及其与LUAD患者临床特征的关联。此外，检测LUAD细胞系中miR-1293的表达。用miR-1293模拟物或拮抗剂转染LUAD细胞后，测量细胞活力、迁移、侵袭以及MMP2和MMP9的表达。在TCGA数据库中，磷酸葡萄糖变位酶（PGM）5被确定与LUAD患者的miR-1293呈负相关，它们之间的关联由Targetscan软件预测。因此，我们进一步验证了miR-1293与PGM5之间的关系。此外，在异种移植小鼠模型中验证了miR-1293的作用和机制。
我们发现，LUAD患者和细胞系中miR-1293表达升高，但PGM5降低。较高的miR-1293表达与LUAD患者的病理分期和较差的总生存期呈正相关。miR-1293模拟物显著促进，而miR-1293拮抗剂抑制LUAD细胞的活力、迁移、侵袭以及MMP2和MMP9的表达。PGM5是miR-1293的靶点。PGM5的过表达消除了miR-1293对LUAD细胞恶性表型的影响。给予miR-1293拮抗剂可减小肿瘤体积，降低Ki-67和MMP9的染色，但提高PGM5表达。
miR-1293通过靶向PGM5促进LUAD细胞的增殖、迁移和侵袭，这表明miR-1293可能成为LUAD患者的潜在治疗靶点。
