关键词: 肺腺癌, lncRNA PKD2-2-3, 细胞迁移, 细胞侵袭, 上皮间质转化

Abstract:

Background and purpose: Long non-coding RNA (lncRNA) is abnormally expressed in lung adenocarcinoma patients, and closely related to tumor occurrence, development and chemotherapy resistance. In this study, we mainly investigated the biological function of lncRNA PKD2-2-3 and verified its effect on the proliferation, colony formation, migration and invasion in lung adenocarcinoma. Methods: Three pairs of lung adenocarcinoma tissues and adjacent tissues were analyzed based on expression profiling Affymetrix® GeneChip Human Transcriptome Array 2.0 (HTA2.0), and we focused on lncRNA PKD2-2-3 that showed most significant difference between lung adenocarcinoma issues and adjacent tissues. Besides, we found the upregulated expression of lncRNA PKD2-2-3 in lung adenocarcinoma tissues and suggested the relation of lncRNA PKD2-2-3 expression with prognosis by using GSE19188 and GSE30219 data in Gene Expression Omnibus (GEO) database. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of lncRNA PKD2-2-3 in cell lines including HBE, A549 and PC9. After using siRNAs to decrease the expression of lncRNA PKD2-2-3 in A549 and PC9, we detected cell proliferation and colony formation by cell counting kit-8 (CCK-8) assay and colony formation assay. Effects of lncRNA PKD2-2-3 on migration and invasion in lung adenocarcinoma cells were detected by wound-healing assay and transwell assay, respectively. Moreover, we detected expression levels of E-cadherin and N-cadherin that were epithelial-mesenchymal transition (EMT) related genes by Western blot. The effect of lncRNA PKD2-2-3 on the formation and growth of lung adenocarcinoma in vivo was verified by subcutaneous transplantation tumor model. Results: LncRNA PKD2-2-3 was highly expressed in lung adenocarcinoma tissue, and was positively associated with poor prognosis of lung adenocarcinoma patients. Compared with human bronchial epithelial cells (HBE), lncRNA PKD2-2-3 was overexpressed in A549 and PC9. The proliferation, colony formation, migration and invasion of lung adenocarcinoma cells were significantly inhibited when decreasing the expression level of lncRNA PKD2-2-3. Western blot also showed that the expression level of E-cadherin was increased, while the level of N-cadherin was decreased after lncRNA PKD2-2-3 knockdown. Subcutaneous tumor transplantation experiments showed that lncRNA PKD2-2-3 knockdown inhibited the growth of lung adenocarcinoma in vivo. Conclusion: LncRNA PKD2-2-3 expression was upregulated in lung adenocarcinoma tissues, and it was associated with poor prognosis of lung adenocarcinoma patients. Overexpression of lncRNA PKD2-2-3 promoted the proliferation, colony formation, migration and invasion of lung adenocarcinoma cells. LncRNA PKD2-2-3 level was closely related to EMT process in lung adenocarcinoma in vitro and in vivo.

Key words: Lung adenocarcinoma, LncRNA PKD2-2-3, Cell migration, Cell invasion, Epithelial-mesenchymal transition