lncRNA RP11-838N2.3 Promoted Cisplatin Resistance in Lung Adenocarcinoma

Abstract EN

The mechanism of RP11-838N2.3 promoting cisplatin resistance in lung adenocarcinoma (LAD) was unclear.

The RP11-838N2.3 expression level in cells and LAD tissues was detected by qPCR.

We constructed lentivirus-mediated GV303 overexpression and GV248 shRNA vector targeting RP11-838N2.3, then infected A549 and A549/DDP cell and furtherly analyzed cell biology.

High-throughput gene chip analysis showed that RP11-838N2.3 was significantly upregulated in A549/DDP (change fold=66.056595).

The qPCR results showed that the expression level of RP11-838N2.3 in A549/DDP cell was significantly higher than that in A549 cells (P<0.05), and the expression level of RP11-838N2.3 in LAD tissues was also significantly higher than that in adjacent tissues (P<0.05).

The expression level of RP11-838N2.3 in cisplatin-insensitive LAD tissues was also significantly higher than that in cisplatin-sensitive LAD tissues (P<0.05).

Survival analysis showed that OS (overall survival) and DFS (progression-free survival) of high RP11-838N2.3 expression in the cisplatin-sensitive or cisplatin-insensitive LAD group were lower (P<0.001 and P<0.001) than those of low RP11-838N2.3 expression in the cisplatin-sensitive or cisplatin-insensitive LAD group.

CCK8 showed that the OD450 value of RP11-838N2.3 overexpression increased significantly at 24 h, 48 h, and 72 h after transfection, while the knockdown of RP11-838N2.3 caused OD450 value at 24 h, 48 h, and 72 h after transfection significantly reduced, under the action of cisplatin that had the same trend (P<0.05).

The cell migration showed that the RP11-838N2.3 overexpression increased significantly migration activity and RP11-838N2.3 knockdown inhibited migration activity at 24 h, 48 h, and 72 h after transfection.

The same trend was also observed under the action of cisplatin (P<0.05).

The cell invasion showed that the invasion rate of RP11-838N2.3 overexpression increased significantly, while the invasion rate of RP11-838N2.3 knockdown decreased significantly, and the same trend was observed under the action of cisplatin (P<0.05).

Apoptosis results showed that the apoptosis rate of RP11-838N2.3 overexpressed cells decreased significantly and the apoptosis rate of RP11-838N2.3 knockdown cells increased significantly, and the same trend was also observed under the action of cisplatin (P<0.05).

However, the results of cell cycle showed that there was no significant difference in the proportion of cells in each phase of the cell cycle after RP11-838N2.3 overexpression or knockdown (P>0.05).RP11-838N2.3 was significantly upregulated in cisplatin-resistant cell and tissues of LAD.

RP11-838N2.3 could enhance the proliferation, migration, and invasion and inhibit apoptosis of LAD cisplatin-resistant cell.

So RP11-838N2.3 could enhance the cisplatin resistance of LAD cells and was a resistant lncRNA molecule.