CSE1L, as a novel prognostic marker, promotes pancreatic cancer proliferation by regulating the AKT/mTOR signaling pathway

Abstract

Pancreatic cancer is one of the most aggressive tumors with poor prognosis and new targetable therapies are urgently required. CSE1L (chromosome segregation 1 like) is thought to play an important role in tumorigenesis and acts as a cancer therapeutic target. However, the biological function and the underlying mechanism of CSE1L in pancreatic cancer are still not fully explicit. In the present study, we found that high CSE1L expression was related to a worse prognosis in patients with pancreatic cancer according to data from the Cancer Genome Atlas (TCGA) database. Additionally, we found that CSE1L knockdown inhibited the proliferation of pancreatic cancer cells and promoted apoptosis, while CSE1L overexpression demonstrated the opposite phenomenon. Furthermore, we discovered that CSE1L might regulate pancreatic cancer proliferation through AKT signaling pathway. In summary, we reveal that CSE1L plays a crucial role in tumor growth and may serve as a potential prognostic and therapeutic target for pancreatic cancer.

Keywords: AKT/mTOR signaling pathway.; CSE1L; pancreatic cancer; proliferation.

Figure 1

Aberrant expression level of exportins in pancreatic cancer patients. (A) Heatmap of the seven exportins mRNA expression in GSE16515. (B) The mRNA expression of seven exportins in pancreatic cancer tissues assessed using data from GSE16515. (C) Expression panels for seven exportins comparing the data between 4 normal individuals and 178 pancreatic cancer patients in the TCGA database. (D) Seven exportins mRNA expression levels in 20 different cancer types by using the ONCOMINE database. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

CSE1L is significantly overexpressed in both pancreatic cancer tissues and cell lines. (A)The prognostic value of the CSE1L expression level in pancreatic cancer patients; the survival curve was plotted utilizing the UALCAN database. (B) Relationship between the CSE1L expression level and pancreatic cancer clinical stages. (C) CSE1L is overexpressed in pancreatic cancer tissues. (D) CSE1L is overexpressed in pancreatic cancer cell lines.

Figure 3

Knockdown of CSE1L inhibits pancreatic cancer cell growth. (A) Western blot analyses showing the efficiency of CSE1L knockdown in PANC1 cells and AsPC1 cells, respectively. (B and C) Knockdown of CSE1L significantly suppressed the proliferation of PANC1, AsPC1 and CFPAC1 cells by CCK8 and colony formation assays. Data are representative of results from three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 4

Overexpression of CSE1L promoted pancreatic cancer growth. (A)Western blot analyses showing the efficiency of CSE1L overexpression in PANC1 cells and AsPC1 cells, respectively. (B and C) Overexpression of CSE1L significantly promoted proliferation in PANC1 and AsPC1 cells by CCK8 and colony formation assays. Data are representative of results from three independent experiments. (D) CSE1L increases pancreatic cancer growth in vivo.*P < 0.05, **P < 0.01, ***P < 0.001.

Figure 5

CSE1L influences apoptosis of pancreatic cancer cells. (A) CSE1L knockdown in PANC1, AsPC1 and CFPAC1 cells significantly increased the percentage of apoptotic cells. (B) Overexpression of CSE1L significantly decreased the percentage of apoptotic cells. *P < 0.05, **P < 0.01.

Figure 6

CSE1L regulates the AKT signaling pathway in pancreatic cancer cells. (A) Western blot analysis of p-AKT, AKT, p-mTOR and mTOR in cells transfected with CSE1L siRNAs. (B) Western blot analysis of p-AKT, AKT, p-mTOR and mTOR in cells stably over-expressing CSE1L. *P < 0.05, **P < 0.01.