Transcriptome sequencing analysis reveals unique and shared antitumor effects of three statins in pancreatic cancer

Abstract

Statins, a class of commonly prescribed cholesterol-lowering medications, have been revealed to influence the risk of multiple types of cancer. However, the antitumor effects of statins on pancreatic cancer and their differential efficacy among a variety of statins are not currently well-defined. The aim of the present study was therefore to identify and compare the genes and related biological pathways that were affected by each individual statin on pancreatic cancer. Two human pancreatic cancer cell lines, MiaPaCa2 and PANC1, were exposed to three statins, lovastatin, fluvastatin and simvastatin. The inhibitory effect of statins on pancreatic cancer cell proliferation was first validated. Next, RNA-seq analysis was used to determine the gene expression alterations in either low (2 µM) or high (20 µM) statin concentration-treated cancer cells. Marked differences in gene transcription profiles of both pancreatic cancer cell lines exposed to high concentration statins were observed. Notably, the high concentration statins significantly suppressed core-gene CCNA2-associated cell cycle and DNA replication pathways and upregulated genes involved in ribosome and autophagy pathways. However, the low concentration statin-induced gene expression alterations were only detected in MiaPaCa2 cells. In conclusion, a marked difference in the intra and inter cell-type performance of pancreatic cancer cells exposed to a variety of statins at low or high concentrations was reported herein, which may provide insights for the potential clinical use of statins in future pancreatic cancer therapeutics.

LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer

“…Raw sequence data of cancer cell line treated with Metformin and simvastatin were generated from NCBI GEO data base with accession number GSE146982, GSE141052 and GSE149566 [ 81 , 82 ]. LCT analysis was performed with ReFuse and the overall LCT levels was summarized by adding up all the junction reads supporting LCT events and normalized with the read depth in each sample.…”

Polysaccharide Chiral Stationary Phases for the Achiral and Chiral Separation of Cannabinoids

“…Further advancements in the production of the CSPs added robustness and increased solvent compatibility, via the incorporation of an immobilization step. This immobilization step both cross-links the polysaccharide backbone and bonds it to the silica gel surface, leading to the insolubilization of the polymer [23][24][25][26][27][28][29][30][31][32]. This resulted in a new generation of immobilized CSPs, providing access to selectors that were previously not accessible and an expanded range of compatible solvents for expanded selectivity (see Figure 2 for full list of immobilized CSP selectors as of the time of this publication).…”

Pathway-Based Drug Repurposing with DPNetinfer: A Method to Predict Drug–Pathway Associations via Network-Based Approaches

“…For instance, pravastatin could inhibit cell proliferation by increasing MAT1A expression in cancer cell lines, 38,39 while simvastatin was found to suppress breast cancer with tumor vascular normalization. 40,41 Sitagliptin would affect gastric cancer cells proliferation by suppressing melanomaassociated antigen-A3 expression. 42 In another network-based drug repurposing approach we developed for prediction of ATC codes, 24 a very good consistency (62% coverage with L ≤ 3) was obtained with this DPNetinfer method (Table S8).…”