SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Serpin peptidase inhibitor clade H member 1 (SERPINH1) was initially recognized as an oncogene implicated in various human malignancies. Nevertheless, the clinical relevance and functional implications of SERPINH1 in colorectal cancer (CRC) remain largely elusive. AIM: To investigate the effects of SERPINH1 on CRC cells and its specific mechanism. METHODS: Quantitative real-time polymerase chain reaction, western blotting analysis, The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues. A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC. RESULTS: SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues, manifested at both mRNA and protein tiers. Elevated SERPINH1 levels correlated closely with advanced T stage, lymph node involvement, and distant metastasis, exhibiting a significant association with poorer overall survival among CRC patients. Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation, invasion, and migration in vitro, while conversely, SERPINH1 knockdown elicited the opposite effects. Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation. Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation, thereby facilitating CRC cell invasion and migration. CONCLUSION: These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC, potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

Knockdown of ZNF479 inhibits proliferation and glycolysis of gastric cancer cells through regulating ß-catenin/c-Myc signaling pathway.

Gastric cancer is the fifth most common malignancy and the third most deadly tumor in the world. Zinc finger protein 479 (ZNF479) has been demonstrated to play crucial roles in hepatocellular carcinoma. However, the function of ZNF479 in gastric cancer remains to be clarified. The current study aimed to investigate the role of ZNF479 in gastric cancer progression and elucidate the potential molecular mechanism. In this study, Cell Count Kit-8 and colony formation assays demonstrated that knockdown of ZNF479 inhibited cell proliferation in AGS and SGC-7901 cells. Of note, knockdown of ZNF479 hinders tumor growth of xenograft tumor mice. What is more, knockdown of ZNF479 inhibited glucose uptake, lactate production, adenosine triphosphate level, and extracellular acidification ratio; increased oxygen consumption ratio in gastric cancer cells; and decreased the expression of glycolytic proteins both in vitro and in vivo. Furthermore, analysis mechanism suggests that ZNF479 participated in the regulation of gastric cancer progression through affecting the ß-catenin/c-Myc signaling pathway. Collectively, ZNF479 plays a role as an oncogene through modulating ß-catenin/c-Myc signaling pathway in the development of gastric cancer, which provides a new research target for future studies.