LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2

Long non-coding RNAs (lncRNAs) have been proved to be involved in the occurrence and progression of various tumors including pancreatic cancer (PC). Growing evidence shows that lncRNA X inactive-specific transcript (XIST) functions as an oncogene in multiple tumorigenesis. However, the underlying mechanism of lncRNA XIST in the progression of PC remains elusive.

Taken together, our study demonstrated that lncRNA XIST functions as an oncogene and exerts its regulation via miR-185-5p/CCND2 axis, promoting proliferation and inhibiting apoptosis in PC.

Expression levels of XIST and miR-185-5p both in PC tissues or PC cells were determined using real-time quantitative PCR (qRT-PCR). Gain and loss-of-function of XIST or miR-185-5p was performed for further exploration. Moreover, colony formation assay was performed to assess cell proliferation. Flow cytometry analysis was performed to measure cell cycle and apoptosis. Dual-luciferase reporter assay was conducted to verify the correlation between XIST, miR-185-5p and CCND2, respectively. Additionally, western blot analysis was conducted to determine the expression pattern of apoptosis-related proteins and cell cycle-associated proteins.

Herein, we found that XIST expression was up-regulated while miR-185-5p was down-regulated both in PC tissues and cell lines, compared with that of controls. Moreover, there was a negative correlation between XIST and miR-185-5p. Following that, functional experiments displayed that knockdown of XIST or overexpression of miR-185-5p inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis in PC cells. Furthermore, mechanistic experiments displayed that XIST could negatively regulate miR-185-5p via direct binding. In addition, CCND2 was shown to be a downstream target of miR-185-5p. Importantly, overexpression or knockdown of XIST significantly increased or decreased the expression of CCND2, while these effects were reversed by miR-185-5p. Conclusions: Taken together, our study demonstrated that lncRNA XIST functions as an oncogene and exerts its regulation via miR-185-5p/CCND2 axis, promoting proliferation and inhibiting apoptosis in PC.