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Gene mutation and pathogenesis bacteria are highly associated with colorectal cancer (CRC) development and progression. Autophagy is a self-clearance pathway to degrade abnormal proteins and infected bacteria in cells. Autophagy plays a dual role in cancer development. Among the autophagy-related (ATG) proteins, ATG5 is the key component required for the core machinery of autophagy. However, the role of ATG5 in CRC malignancy remains unclear. Herein, we found that a high ATG5 protein level was correlated with poor overall survival (OS) and disease-free survival (DFS) of 118 patients with CRC. After stratification with demographic and clinicopathologic factors, a high ATG5 protein level was significantly correlated with unfavorable overall survival in female and elder (>60 year) CRC patients and tumor tissues with poor differentiation, late T stages (III + IV), whereas the ATG5 protein level was positively associated with the overall survival in CRC patients without lymph node invasion and radiation therapy. In contrast, a high ATG5 protein level was significantly associated with worse DFS in CRC patients with early stage of AJCC and no radiation therapy. In addition, colorectal cancer cells stably harboring small interfering RNA (siRNA) against ATG5 diminished the tumorsphere formation and sensitized cancer cells to chemotherapeutic agents. Taken together, our results suggest that ATG5 might be a prognostic biomarker for CRC and a potential therapeutic target for CRC patients. more...

Purpose: To investigate the association of autophagy-related gene expression with age-related macular degeneration (AMD). Methods: Patients with AMD were recruited for analysis by conjunctival impression cytology. mRNA was assessed by real-time polymerase chain reaction (RT-PCR) to evaluate whether the expression of 26 autophagy-related genes (ATGs) was correlated with AMD. Further studies on cell viability and autophagic flux in response to oxidative stress by H2O2 were performed in human retinal pigment epithelial (RPE) cell lines based on the results of impression cytology. Results: Both the neovascular AMD (nAMD) and polypoidal choroidal vasculopathy (PCV) groups had significantly higher mRNA levels of gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) than the control group, but there was no significant difference between these two groups. Age difference existed only in the AMD group. GABARAPL1 and MAP1LC3B mRNA expression increased significantly after acute oxidative stress in adult retinal pigment epithelial (ARPE-19) cells. Cell viability significantly increased and decreased in the cells harboring GABARAPL1 expression vector and silenced with siRNA against GABARAPL1, respectively, during short-term oxidative stress, whereas viability increased in the GABARAPL1-silenced cells after long-term oxidative stress. Silencing GABARAPL1 itself caused a reduction in autophagic flux under both short and long-term oxidative stress. Conclusion: Our study showed the possibility of assessing autophagy-related gene expression by conjunctival impression cytology. GABARAPL1 was significantly higher in AMD. Although an in vitro study showed an initial protective effect of autophagy, a cell viability study revealed the possibility of a harmful effect after long-term oxidative injury. The underlying mechanism or critical factors require further investigation. more...