Knockdown of PNO1 inhibits esophageal cancer progression.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang G
PROVIDER: S-EPMC8025143 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. Nevertheless, the molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown. METHODS:qRT-PCR assay or western blot analysis was performed to assess the expression level of SETDB1 mRNA or protein, respectively. siSETDB1, pCMV6-XL5-SETDB1, miR-381-3p mimic, or miR-381-3p inhibitor was transfected into cells to regulate the expression of SETDB1 or miR-381-3p. MiRNA directly interacted with SETDB1 was verified by luciferase reporter assay and RNA immunoprecipitation. CCK-8 assay, colony formation assay, flow cytometric analysis, and transwell assay were used to detect the abilities of cell proliferation, cell cycle progression and migration, respectively. Animal model of xenograft tumor was used to observe the regulatory effect of SETDB1 on tumor growth in vivo. RESULTS:We verified that SETDB1 mRNA level was upregulated in breast cancer tissues and cell lines, and SETDB1 depletion led to a suppression of cell proliferation, cell cycle progression and migration in vitro, as well as tumor growth in vivo. SETDB1 was verified to be a target of miR-381-3p. Moreover, miR-381-3p overexpression suppressed cell proliferation, cell cycle progression and migration, whereas SETDB1 abated miR-381-3p-mediated regulatory function on breast cancer cells. CONCLUSIONS:This study revealed that SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy.
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Project description:BackgroundA glioma is a tumor originating from glial cells in the central nervous system. Although significant progress has been made in diagnosis and treatment, most high-grade glioma patients are prone to recurrence. Therefore, molecular targeted therapy may become a new direction for adjuvant therapy in glioma. In recent years, many studies have revealed that circular RNA (circRNA) may play an important role in the occurrence and development of many tumors including gliomas. Our previous study found that the expression of hsa_circ_0008922 was up-regulated in glioma tissues upon RNA sequencing. The biological mechanism of circ_0008922 is still unreported in gliomas. Therefore, in this study, we preliminarily outlined the expression of hsa_circ_0008922 in glioma and explored its biological functions.MethodsThe expression of hsa_circ_0008922 in forty glioma tissues and four glioma cell lines (A172, U251, SF763 and U87) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between hsa_circ_0008922 expression and clinicopathological features of glioma patients was evaluated by Fisher's exact test. To understand the potential function of hsa_circ_0008922 in glioma, we constructed small interfering RNA (siRNA) to hsa_circ_0008922 to downregulate its expression in glioma cell lines A172 and U251. With these hsa_circ_0008922 downregulated cells, a series of assays were carried out as follows. Cell proliferation was detected by CCK8 assay, migration and invasion were determined by wound healing assay and transwell assay, respectively. Colony formation ability was evaluated by plate clonogenic assay. Moreover, flow cytometry combined with Western blot was performed to analyze apoptosis status and the expression of apoptotic related proteins (caspase 3 and caspase 9). Finally, the possible biological pathways and potential miRNA targets of hsa_circ_0008922 were predicted by bioinformatics.ResultsWe found that the expression of hsa_circ_0008922 in glioma tissues was 3.4 times higher than that in normal tissues. The expression of has_circ_0008922 was correlated with WHO tumor grade. After down-regulating the expression of hsa_circ_0008922, malignant biological behavior of glioma cells was inhibited, such as cell proliferation, colony formation, migration, and invasion. At the same time, it also induced apoptosis of glioma cells. Predicted analysis by bioinformatics demonstrated that hsa_circ_0008922 may be involved in tumor-related pathways by acting as a molecular sponge for multiple miRNAs (hsa-let-7e-5p, hsa-miR-506-5p, hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7a-5p). Finally, we integrated our observation to build a circRNA-miRNA-mRNA predictive network.
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Project description:Purpose: The objective of this study was to examine the expression and role of Centromere protein W (CENPW) in bladder cancer (BLCA), as well as its potential mechanistic impact on the progression of BLCA. Methods: In this study, we conducted a comparative analysis of the mRNA expression level of CENPW in BLCA tissues and adjacent normal tissues using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we investigated the association between CENPW expression and patient prognosis. Furthermore, we performed in vitro and in vivo experiments to assess the impact of CENPW knockdown on various tumor biological phenotypes in BLCA. Finally, we conducted an analysis to elucidate the underlying mechanisms responsible for the observed phenotypic alterations in BLCA. Results: The expression of CENPW was found to be upregulated in BLCA, and its higher expression was associated with a poorer disease-specific survival (DSS). CENPW was found to have close associations with the cell cycle, mitosis, and DNA replication. In vitro and in vivo experiments demonstrated that the inhibition of CENPW led to a suppression of BLCA progression. Specifically, the knockdown of CENPW resulted in cell cycle arrest phase and induced apoptosis in BLCA by potentially inactivating the signal transducer and activator of transcription3 (STAT3) signaling pathway. Conclusion: CENPW has the potential to function as a molecular marker indicating an unfavorable prognosis in BLCA. Additionally, CENPW exhibits promise as a novel therapeutic target for BLCA.
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