Aim: The present study explored the clinical significance of microRNA-22 (miR-22) expression in lung squamous cell carcinoma and to explore the targeting relationship with vascular endothelial growth factor receptor 3 (VEGFR3).

Methods: A total of 49 patients with lung squamous cell carcinoma who underwent surgical treatment were selected. The expression of miR-22 was detected by fluorescence quantitative realtime PCR (qPCR), the expression of VEGFR3 was detected by Western blotting assays, and D240 labeled microlymphatic vessels density (MLVD) was detected by immunohistochemistry (IHC). Lung squamous cell carcinoma cell line SK-MES-1 was selected and the targeting relationship between miR-22 and VEGFR3 was analyzed by double luciferase reporter gene assay. Western blotting assays were used to detect the expression of vascular endothelial growth factor-D (VEGFD) and D240 in the blank control group, empty vector transfection group, miR-22 transfection group, miR-22 and VEGFR3 co-transfection group.

Results: The expression range of miR-22 in lung squamous cell carcinoma was 0.8-3.5. The expression of miR-22 in lung squamous cell carcinoma was significantly different by tumor maximum diameter, lymph node metastasis, vascular invasion and TNM stage. The expression of miR-22 was linked to survival time. There was a negative correlation between miR-22 and VEGFR3, miR-22 and MLVD. Double luciferase reporter gene assays showed that miR-22 reduced the luciferase activity of pGL3-VEGFR3-WT transfected cells. Compared with the control group, the expression of VEGF-D and D2-40 in the miR-22 transfection group was significantly decreased. However, VEGF-D and D240 in the miR-22 and VEGFR3 co-transfection group reversed the changes.

Conclusion: We assumed that the abnormal expression of miR-22 in lung squamous cell carcinoma may be involved in the development and progression of lung squamous cell carcinoma. MiR-22 negatively regulated the target gene VEGFR3 to mediate lymphangiogenesis. The expression of miR-22 may also be linked to the prognosis of the disease.

目的：本研究探讨microRNA-22（miR-22）在肺鳞癌中表达的临床意义，并探讨其与血管内皮生长因子受体3（VEGFR3）的靶向关系。

方法：共选择接受手术治疗的肺鳞癌患者49例。采用荧光定量实时PCR（qPCR）检测miR-22的表达，Western blotting检测VEGFR3的表达，免疫组织化学（IHC）检测D240标记的微淋巴管密度（MLVD）。选择肺鳞状细胞癌细胞系SK-MES-1，通过双荧光素酶报告基因检测分析miR-22与VEGFR3的靶向关系。Western blotting法检测空白对照组、空载体转染组、miR-22转染组、miR-22和VEGFR3共转染组血管内皮生长因子-D（VEGFD）和D240的表达。

结果：miR-22在肺鳞癌中的表达范围为0.8-3.5。miR-22在肺鳞癌中的表达因肿瘤最大直径、淋巴结转移、血管侵犯和TNM分期而异。miR-22的表达与存活时间有关。miR-22与VEGFR3、miR-22与MLVD呈负相关。双荧光素酶报告基因分析表明，miR-22 降低了 pGL3-VEGFR3-WT 转染细胞的荧光素酶活性。与对照组相比，miR-22转染组VEGF-D和D2-40的表达明显降低。然而，miR-22和VEGFR3共转染组中的VEGF-D和D240逆转了这种变化。

结论：我们推测miR-22在肺鳞癌中的异常表达可能参与了肺鳞癌的发生发展。MiR-22 负调控靶基因 VEGFR3 以介导淋巴管生成。miR-22的表达也可能与疾病的预后有关。