HIF1A expression

This research contributed to the growing body of evidence supporting the role of metabolic modulators in cancer therapy and emphasized the importance of understanding tumor microenvironments to optimize treatment outcomes. However, the need for further research into the metabolic pathways is underscored to enhance therapeutic strategies for cancer treatment.

The Drosophila melanogaster gene similar ( sima ), which encodes the sole fly ortholog of Hif1α, is required to up-regulate glycolysis in preparation for larval growth. sima mutant larvae exhibit severe defects in carbohydrate metabolism and die during the second larval instar. sima mutant larvae exhibit the same metabolic phenotypes as Drosophila Estrogen Related Receptor ( dERR ) mutants, suggesting that these two transcription factors coordinately regulate the larval glycolytic program. Sima/Hif1α and dERR accumulation is mutually dependent, as loss of either transcription factor results in decreased abundance of the other.

Hypoxia-induced high HIF-1α expression upregulated YTHDF2 through hH3K18la modification, enhanced YTHDF2-BNIP3 interaction, and regulated BNIP3-dependent mitophagy-mediated metabolic reprogramming to affect glioma proliferation and invasion.

Both MEK1/ERK and PI-3 K/Akt SPW play crucial roles in bFGF-mediated HIF-1 activation. BFGF had a notable activation of HIF-1. PI-3 K/Akt and MEK1/ERK SPW worked together to regulate this process by various mechanisms.

We also discuss the canonical and non-canonical regulation of HIF-1α and HIF-2α under hypoxic and normal conditions. Finally, we outline recent strategies aimed at targeting HIF-1α and/or HIF-2α.

Furthermore, morusin effectively reversed EMT induced by phospho-STAT3 or HIF-1α. Morusin has a reversing effect on the EMT of gallbladder cancer cells by modulating STAT3/HIF-1α signaling.

Nuclear circHIF-1α interacted with human antigen R protein (HUR) to increase HIF-1α expression. Thus, our results demonstrated that circHIF-1α ameliorates senescence and exacerbates growth in PC cells by increasing HIF-1α through targeting miR-375 and HUR, suggesting that targeting circHIF-1α offers a potential therapeutic candidate for PC.

Clinical data demonstrate circPLOD2a and b are highly expressed in GBM negatively correlated with XIRP1, whose lower expression associates with higher glioma grade and worse prognosis. In conclusion, hypoxia-induced circPLOD2a and b are oncogenic regulators of tumour aggressiveness through attenuating the interaction between HuR and XIRP1 in glioblastoma cells and may be potential therapeutic targets for this disease.

Enrichment analysis indicated enrichment of these hub targets in the programmed cell death-ligand 1 (PD-L1) checkpoint, phosphatidylinositol 3-kinases/protein kinase B (PI3K-Akt), Ras, and hypoxia-inducible factor-1 (HIF-1) signalling pathways with significant cut-offs of FDR < 0.01 and p < 0.05. Therefore, network pharmacology and molecular docking analyses revealed that dehydroxy-isocalamendiol and spathulenol exert therapeutic efficacy on gastric cancer by multiple targets, NFKB1 and HIF1A, and pathways (MAPK, PD-L1 checkpoint, PI3K-Akt, Ras, and HIF-1 pathways).

In conclusion, the ergosteroids present in marine sponge C. aerizusa extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.

Furthermore, in vivo administration of PYZ promotes the infiltration of CD8+ T cells into the tumor and inhibits tumor growth, an effect that is attenuated in Nude mice or mice with CD8+ T cell depletion or deficiency of Ifnar. Overall, our findings showed that pyrithione zinc could trigger tumor immunogenicity by downregulating MMR machinery and activating STING pathway in tumor cells, and provide a translational approach to improve immunotherapy on pMMR cancer.

Notably, inhibition of FBXO22 enhances the efficacy of Lenvatinib both in vitro and in vivo. Therefore, FBXO22 may present itself as a potential target for therapeutic intervention in the treatment of HCC.

RNA-seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1-dependent mechanism in TFE3-RCC. Our data suggest that the coordinated metabolic shift via the PRCC-TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC-TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3-RCC.

These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.

According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method...Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.

Additionally, BBR inhibited tumor growth in nude mice. In conclusion, BBR exerts antitumor effects through upregulating HIF-1α and could be used as a therapeutic agent for HCC.

Additionally, we observe a positive correlation between SEPT5 overexpression and resistance to sorafenib and sunitinib in ccRCC cells. Ultimately, knockdown of SEPT5 significantly inhibits xenografted tumor growth in vivo. Overall, this study provides compelling evidence that directly targeting the HIF-1α-SEPT5 feedback axis may be an effective approach for suppressing the proliferation and progression of ccRCC, offering new insights into the diagnosis and treatment of ccRCC patients.

The combination treatment also reduced the expression of angiogenesis-related factors VEGF-A and HIF-1α. This comprehensive study provides substantial evidence for the potential of VCA and cisplatin combination therapy in TNBC treatment and underscores the significance of integrating 2D and 3D models in preclinical cancer research.

Furthermore, PX-478 could suppress the expression of HIF-1α and vascular endothelial growth factor-A (VEGF-A), but BPRC0261 only suppressed VEGF-A. Taken together, this innovative 3D NIR-II imaging system combining the biocompatible Pdots with unique optical specificity enables non-invasive, real-time monitoring the efficacy of anti-angiogenic compounds.

Additionally, glycolytic enzymes were upregulated in the skeletal muscles of miR-204-injected mice. These findings suggest a novel physiological role for miR-204 in promoting skeletal muscle glycolysis, particularly in situations where insulin action is limited.

Furthermore, a positive correlation was observed between the expression levels of HIF-1α and CD47 in GBM. Lentivirus-mediated knockdown of HIF-1α protein and plasmid-based overexpression of CD47 protein simultaneously enhanced cell proliferation, clonogenic potential and cell migration abilities in GBM, and HIF-1α was found to regulate key pathways, including the P-PI3K/P-AKT, SOX2/OCT4 and MMP2/MMP9 pathways, in GBM.

In addition, SNF can reduce the activity of Matrix Metallopeptidase (MMP-2/9), and inhibit hypoxia-inducible factor-1α (HIF-1α) expression by regulating the downstream PI3K/AKT and Ras/MAPK pathways, thereby preventing vascular endothelial growth factor (VEGF) production, and further inhibits VEGF receptor-2 activation and ultimately inhibits angiogenesis in HT1080 and HUVECs. Therefore, SNF has the potential to develop tumor prevention functional substances and can provide theoretical basis for the high-value comprehensive utilization of brown algae.

The differential responses observed emphasize the need for tailored preconditioning strategies for specific cell types. These findings underscore the importance of hypoxic preconditioning and warrant further research into the underlying mechanisms, bringing us closer to effective neurological disorder treatments.

Our findings indicate that MTX may have a novel role as an established drug in p53 wild-type NSCLC tumor therapy by down-regulating miR-20b expression. These findings are expected to provide preclinical evidence for miR-20b-targeting NSCLC therapeutic strategies.

PKM2/HIF-1α-axis-dependent glycolysis participates in the pathogenesis of EP combined with endometriosis by mediating TGF-β1 signaling.

Decitabine combined with LW6 upregulated PER3, downregulated HIF-1α, and inhibited lymph node metastasis of OSCC in nude mice. Our findings reveal the role and mechanism of HIF-1α regulation by PER3 and support the potential clinical application of targeting PER3 in treating OSCC metastasis.

However, it is essential to consider the potential risks associated with CM and CE treatment on ASCs, as well as the potential recruitment of ASCs by cancer tumors and the risks associated with this recruitment. Further research is needed to elucidate these potential risks and benefits.

The study's outcomes demonstrated that the introduction of Clostridium novyi-NT spores triggered apoptosis in cervical cancer cells (derived from the TC-1 cell line) via the mitochondrial pathway, subsequently resulting in tumor regression in a mouse model.

BC-PDA/HA could also effectively improve hypoxia and inhibit tumor angiogenesis to enhance PDT efficacy, demonstrating synergistic chemo-PDT activity. In conclusion, this work provided a novel strategy for synergistic chemo-photodynamic therapy against breast cancer.

PHPS1 can enhance PD-L1 serine phosphorylation by regulating SHP-2/AMPK activity to promote apoptosis of oral squamous cell carcinoma cells under hypoxic conditions.

The diagnostic efficacy was significantly improved with combination of R2 * and Kep. Quantitative parameters by ESWAN and DCE-MRI showed significant differences between EC patients with low and high expression of HIF-1α, and the combination of ESWAN and DCE-MRI improves the efficacy in prediction of HIF-1α expression in EC, which has an excellent clinical application prospect.

These findings revealed novel molecular mechanisms underlying JAK2 LOF mutations-driven endometrial tumorigenesis and revealed that the HIF-1α pathway may be a potential therapeutic target in JAK2-mutated endometrial cancer.

The effects of HIF1α on cell autophagy were assessed in normoxic or hypoxic treatments using KC7F2 (HIF-1 channel inhibitor) or chloroquine (autophagy inhibitor)...The autophagy level of PC cells transfected with oe-HIF1α was increased, with reduced MHC-I expression on cells (membranes), which impaired the cytotoxicity of CD8+ T cells, and thus decreasing the probability of recognition and attack by CD8+ T cells when co-cultured with them. In mice, overexpression of HIF1α hindered the immune suppressive function of CD8+ T cells and facilitated the immune escape of PC by reducing antigen presentation of MHC-I.Under hypoxia, HIF1α-induced autophagy reduces the cytotoxicity of CD8+ T cells by repressing MHC-I expression.

Our findings demonstrate that tumor antigens enriched with HIF-1α may encompass tumor-specific antigens capable of stimulating DC activation, thereby enhancing T cell proliferation and cytotoxicity. These results provide support for the further advancement of HIF-1α enriched tumor antigens in preclinical and clinical investigations pertaining to tumor treatment.

We highlighted distinct metabolic profiles among testicular germ cell tumor subtypes, particularly the prominent glycolytic activity in embryonal carcinomas, with higher hypoxia and reliance on lactate transport. Metabolic reprogramming in embryonal carcinoma may underlie the high proliferation of this tumor subtype, which frequently discloses necrosis. These findings suggest that targeted agents such as MCT1 inhibitors may be particularly useful for treating testicular germ cell tumors containing high proportion of embryonal carcinoma.

Our current research demonstrates the great potential of CD73 inhibitor for clinical translation of cancer studies by analyzing the behavior and function of 3D tumor cells, and thus for more effective treatment protocols for GBM.

Our findings suggest that the AGT-HIF-1α-HILPDA pathway promotes radioresistance in NPC by enhancing lipid droplet accumulation, thereby suppressing ferroptosis. Targeting local Ang II alongside ferroptosis induction offers a promising strategy to improve radiosensitivity in NPC.

Retinoic acid has short-term effect on the proliferation of SH-SY5Y neuroblastoma cells. It was observed that short-term retinoic acid treatment improved neurodegeneration parameters, but it decreased the proliferation by inducing mitophagy and apoptosis of SH-SY5Y neuroblastoma cells.

The machine learning-based pathomics model effectively predicts the OS of ccRCC patients and differentiates between subtypes. The critical roles of the immune-related gene CTLA4 and the PI3K-Akt, HIF-1, and MAPK signaling pathways offer new insights for further research on the molecular mechanisms, diagnosis, and treatment strategies for ccRCC.

In vivo studies showed that compared to the model group, osthole-fed animals significantly reduced tumor weight and volume, inhibited tumor growth, and promoted tumor apoptosis, and the results showed a dose-dependent trend. The study suggested that osthole could inhibit the proliferation and migration of HCT116 cells in CRC, and its mechanism may be related to the regulation of the PI3K/Akt signaling pathway and the expression of core targets.

Our meta-analysis robustly establishes that IH, independently of other confounders, has a strong effect on the brain by inducing oxidative stress, inflammation and apoptosis in rodent models. Our findings support the interest of considering and treating cerebral consequences of OSA in clinical practice.

SHP2 advances CRC progression by modulating TFEB-mediated ferritinophagy, suppressing ROS and ferroptosis. Targeting SHP2 presents a promising therapeutic strategy for CRC.