ABSTRACT
Purpose: This study aimed to investigate the potential role of copine-1 (CPNE1), a calcium-dependent membrane-binding protein encoded by the CPNE1 gene, in colorectal cancer (CRC). Despite previous research on the involvement of copine family members in various solid tumors, the specific role of CPNE1 in CRC remains poorly understood. Methods: We conducted clinicopathological analysis and functional studies to explore the impact of CPNE1 in human CRC. We examined the expression levels of CPNE1 in CRC patients and correlated it with invasive depth, lymph node metastasis, distant metastasis, lymphatic invasion, and TNM stage. Additionally, we performed experiments to assess the functional consequences of CPNE1 knockdown in CRC cells, including proliferation, colony formation, migration, invasion, and the expression of key regulators involved in the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, we evaluated the effects of CPNE1 knockdown on tumor growth using a xenograft mouse model. Results: High expression of CPNE1 was significantly associated with advanced tumor features in CRC patients. CPNE1 knockdown in CRC cells led to impaired abilities in proliferation, colony formation, migration, and invasion. Furthermore, CPNE1 silencing resulted in the suppression of protein expression related to the cell cycle and EMT. In the xenograft mouse model, CPNE1 knockdown inhibited tumor growth. Conclusion: CPNE1 plays a crucial role in promoting tumorigenesis and metastasis in human CRC. By regulating the cell cycle and EMT, CPNE1 influences critical cellular processes at the membrane-cytoplasm interface. These results provide valuable insights into the potential development of novel therapeutic strategies for CRC targeting CPNE1.
ABSTRACT
Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although ß-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of ß-sitosterol effect on the catabolic pathway was not well known. ß-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. ß-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the ß-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when ß-sitosterol was treated. The muscle loss inhibitory efficacy of ß-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. ß-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when ß-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, ß-sitosterol would be a potential treatment agent for aging sarcopenia.
