PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1.

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

The function and mechanism of LAPTM5 in diseases.

The Lysosomal Protein Transmembrane 5 (LAPTM5) is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells. The human LAPTM5 gene is located at position 1p34 and extends approximately 25 kb. Its protein includes five transmembrane domains, three PY motifs, and one UIM. The PY and UIM motifs can interact with various substrates, mediating sorting of proteins from Golgi to lysosome and subsequently participating in intracellular substrate transport and lysosomal stability regulation. Overexpression of LAPTM5 can induce lysosomal cell death (LCD), although the integrity of LAPTM5 protein is necessary for maintaining lysosome stability. Furthermore, LAPTM5 plays a role in autophagy activation during disease processes and has been confirmed to be closely associated with the regulation of immunity and inflammation. Therefore, LAPTM5 regulates a wide range of physiological processes and is involved in various diseases. This article summarizes the characteristics of the LAPTM5 gene and protein structure and provides a comprehensive review of the mechanisms involved in cell death, autophagy, immunity, and inflammation regulation. It emphasizes the significance of LAPTM5 in the clinical prevention and treatment of cardiovascular diseases, immune system disorders, viral infections, cancer, and other diseases, which could provide new therapeutic ideas and targets for human diseases.

Misdiagnosis and delayed diagnosis of atypical autoimmune pancreatitis: Experience from clinical cases.

Autoimmune pancreatitis (AIP) is a fibro-inflammatory disease characterized by inflammation and fibrosis of the pancreas. It is a systemic disease that can affect multiple organs, including the bile ducts, kidneys, lungs, and other organs. However, due to its complex presentation, AIP is often challenging to diagnose, and misdiagnosis with pancreatic tumors can occur. In our study, we reviewed three cases of atypical AIP where patients had normal serum IgG4 levels, leading to initial misdiagnosis with pancreatic tumors. Delayed diagnosis resulted in irreversible pathologies such as retroperitoneal fibrosis. All three patients had bile duct involvement, and imaging findings were similar to those of tumors, further complicating the diagnosis. The correct diagnosis was confirmed only after diagnostic therapy. Our study aims to raise awareness of atypical AIP and improve diagnostic efficiency by analyzing the clinical characteristics of these patients.

The E3 ubiquitin ligase SCF (FBXW10)-mediated LATS2 degradation regulates angiogenesis and liver metastasis in colorectal cancer.

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.