RESUMO
Forkhead box (FOX) transcription factors regulate the development of several human cancers. However, the role and therapeutic potential of FOXA1 in gastric cancer is still largely unexplored. The results showed a significant (P < 0.05) upregulation of FOXA1 in gastric cancer tissues and cell lines. Silencing of FOXA1 in gastric cells significantly (P < 0.05) decreased their viability through induction of apoptosis. The induction of apoptosis was associated with upregulation of Bax and downregulation of Bcl-2. Additionally, FOXA1 silencing caused activation of caspase-3 and 9 with no apparent effects on the expression of caspase-8 suggestive of intrinsic apoptosis. The transwell cell invasion revealed significant (P < 0.05) decline of cell invasion of gastric cancer cells upon FOXA1 silencing. The FOXA1 knockdown further inhibited the in vivo tumor growth suggestive of its therapeutic potential. Taken together, the findings of the present revealed that FOXA1 regulates the proliferation and development of gastric cancer and may exhibit therapeutic implications in gastric cancer treatment.
Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Neoplasias Gástricas/genética , Regulação para Cima , Animais , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Interferência de RNA , Terapêutica com RNAi/métodos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Objective: To study the correlation between gold in GC and biological indicators of gastric cancer (GC) and its effect on prognosis and correlation of POT1-AS1 with GC cellular growth, and to explore its impact in the processes of GC, to supply histological basis for medical treatment of GC. Methods: From September 2019 to December 2021, 80 pairs of GAC specimens and healthy para-carcinoma tissue were immediately stored in paraformaldehyde solution. POT1-AS1 levels in 77 postoperative patients with GC were detected by immunohistochemical method. The correlation of the above indexes and the relationship between the above indexes and the biological behavior and prognosis of GC were analyzed. Results: POT1-AS1 was strongly displayed in GAC specimens, and the difference between groups was statistically significant (P < 0.05). After sh-POT1-AS1 plasmid transfection, the relative expression of POT1-AS1 mRNA in SGC-7901 cells was remarkably lower compared to nontransfection group, and the difference between groups was statistically significant (P < 0.05). After POT1-AS1 knockdown, the SGC-7901 proliferation ability and the number of clones of SGC-7901 decreased remarkably. The relative level of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in SGC-7901 reduced remarkably, while relative expression of cyclin-dependent kinase inhibitor 1A (CDKI1A) increased remarkably, and the difference between groups was statistically significant (P < 0.05). The positive expression of POT1-AS1 was found in GC and stromal cells. TIMP-1 in tumor stromal cells was related to the maximum diameter of tumor (P = 0.027), invasion depth (P = 0.001), lymph node metastasis (P = 0.006), and clinical stages (P = 0.006). TIMP-1 had an effect on the prognosis, while the strong positive group had a poor prognosis. The expression of TIMP-1 in GC cells was not related to clinical biological behavior and prognosis of GC. The VEGF level in GC was correlated to tumor maximum diameter (P < 0.05), invasive depth (P < 0.05), and lymph node metastasis (P < 0.05) that was linked to clinical phases, and the difference between groups was statistically significant (P < 0.05), which was positively correlated with Ki67-LI; the correlation coefficient was 0.254 and P = 0.026, which was not related to the positive expression of TIMP-1 in GC cells and stromal cells. VECF has an effect on the prognosis, and the outcomes of the positive group are worse. Conclusion: The correlation between TIMP-1 of GASTRIC cancer mesenchymal cells of POT1-AS1 and VEGF and Ki-67-Li suggests that TIMP-1 produced by mesenchymal cells can facilitate tumor progression and lead to poor prognosis by promoting tumor cell proliferation. VEGF can strengthen tumor angiogenesis and then promote tumor cell proliferation, which has an adverse effect on the prognosis. Ki-67-LI is correlated to the medical biological behavior and prognosis of the tumor, reflecting the malignant process of the tumor.