Long non-coding RNA-PVT1 promotes migration and metastasis of renal carcinoma cells

Objective To investigate the expression level and clinical significance of long non-coding RNA-PVT1 (Lnc-PVT1) in clear cell renal cell carcinoma (ccRCC).

Methods Sixty-nine pairs of ccRCC tissues and adjacent normal tissues were collected. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of Lnc-PVT1 in ccRCC. RNA in situ hybridization (RISH) was used to determine the positive expression of Lnc-PVT1 in ccRCC. Transwell assay was used to analyze the number of cell migration in ccRCC. The downstream target genes of Lnc-PVT1 and microRNA-145 (miR-145) were predicted by bioinformatics and were verified by experiments. The effects of Lnc-PVT1 on miR-145/matrix metalloproteinase-9 (MMP9) pathway and migration were analyzed by Rescue recovery experiment.

Results The results of qRT-PCR showed that the expression level of Lnc-PVT1 in ccRCC tissues and cells was increased (P < 0.05). RISH assay indicated that Lnc-PVT1 was positively expressed in ccRCC tissue. The positive rate of Lnc-PVT11 in ccRCC tissue was 73.91% (51/69), which was higher than 14.49% of adjacent normal tissues (10/69), the difference was statistically significant (χ²=4.128, P < 0.05). The positive expression of Lnc-PVT1 was correlated with ccRCC pathological grade and lymph node metastasis (P < 0.05), but had no correlations with patient age, sex, tumor size and TNM stage (P>0.05). The results of Transwell migration experiment showed that overexpression of Lnc-PVT1 promoted the migration ability of ccRCC cells, and decreased expression of Lnc-PVT1 inhibited the migration ability of ccRCC cells (P < 0.05). The miR-145 was a target gene regulated by Lnc-PVT1; the downstream direct target gene of miR-145 was MMP9. Lnc-PVT1 could inhibit the expression of miR-145 and promote the expression of MMP9 protein.

Conclusion Lnc-PVT1 promotes migration and metastasis of renal cancer cells through the miR-145/MMP9 pathway. This study may provide a possible molecular target and basis for the treatment of metastatic renal cell carcinoma.