title: The BAX gene as a candidate for negative autophagy-related genes regulator on mRNA levels in colorectal cancer.
abstract: Autophagy is a catabolic process, which is involved in the maintenance of intracellular homeostasis by degrading redundant molecules and organelles. Autophagy begins with the formation of a double-membrane phagophore, followed by its enclosure, thus leading to the appearance of an autophagosome which fuses with lysosome. This process is highly conserved, precisely orchestrated and regulated by autophagy-related genes. Recently, autophagy has been widely studied in different types of cancers, including colorectal cancer. As it has been revealed, autophagy plays two opposite roles in tumorigenesis, as a tumor suppressor and a tumor enhancer/activator, and therefore is called a double-edge sword. Recently, interaction between autophagy and apoptosis has been found. Therefore, we aimed to study the mRNA levels of genes engaged in autophagy and apoptosis in colorectal cancer tissues. Colorectal cancer and adjacent healthy tissues were obtained from 73 patients diagnosed with primary colorectal cancer. Real-time PCR analysis employing Universal Probe Library was used to assess the expression of the seven following selected genes: BECN1, UVRAG, ULK1, ATG13, Bif-1, BCL2 and BAX. For all but one of the tested genes, a decrease in expression was observed. An increase in expression was observed for BAX. BAX expression decreases consistently from early to more advanced stages. High expression of BAX was strongly associated with negative UVRAG expression. The high expression of the BAX gene seems to be a negative regulator of autophagy in colorectal cancer cells. The relative downregulation of autophagy-related genes was observed in colorectal cancer samples.
authors.affiliation: Department of Genetics, Wroclaw Medical University, 50-368, Wroclaw, Poland. justyna.gil@umed.wroc.pl.
authors.forename: Justyna
authors.initials: J
authors.lastname: Gil
authors.affiliation: Department of Operations Research, Wroclaw University of Technology, 50-372, Wroclaw, Poland.
authors.forename: David
authors.initials: D
authors.lastname: Ramsey
authors.affiliation: Department of Genetics, Wroclaw Medical University, 50-368, Wroclaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Szmida
authors.affiliation: Department of Biology and Medical Parasitology, Wroclaw Medical University, 50-345, Wroclaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Leszczynski
authors.affiliation: Department of Genetics, Wroclaw Medical University, 50-368, Wroclaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Pawlowski
authors.affiliation: First Department of Surgical Oncology, Lower Silesian Oncology Center, 53-413, Wroclaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bebenek
authors.affiliation: Department of Genetics, Wroclaw Medical University, 50-368, Wroclaw, Poland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein
keywords: Apoptosis; Autophagy; Colorectal cancer; Relative expression