HIF1A expression

Blockade of Col1 by siRNA or of ITGA3 by a blocking antibody leads to specific inactivation of the FAK/PI3K/AKT/mTOR pathway and impairs malignant tumor behaviors induced by ITGA3. Thus, our data indicate that ITGA3 enhances glycolysis to promote pancreatic cancer growth and metastasis via increasing HIF1α and c-Myc expression in a Col1-dependent autocrine manner, making ITGA3 as a candidate diagnostic biomarker and a potential therapeutic target for pancreatic cancer.

We revealed that the HIF1A inhibitors echinomycin (EC) and YC-1 upregulated CXCL10/11 genes induced by IFN-γ in tumor cells in vitro...Combination therapy enhanced tumor infiltration of CD8 T cells and suppressed tumor angiogenesis. The present study suggests that HIF1A signaling in tumor cells dominates ICI resistance via the downregulation of tumor-derived CXCL10/11.

HMM has potential therapeutic effects on the liver cancer. This study provides important insights regarding the methods for investigating HMM in the treatment of hepatocellular cancer.

First, topotecan hydrochloride (TPT) and vascular endothelial growth factor antisense oligonucleotide (ASOVEGF) were coself-assembled in water through electrostatic interaction to produce chemotherapeutic drug-gene nanoparticles (TPT-ASOVEGF NPs)...In MBC mouse models, the in vivo inhibition rate of TPT-ASOVEGF@MM NPs for lung metastasis was 89.5%, with minor toxic side effects and the least number of metastatic nodules in the lungs. In summary, TPT-ASOVEGF@MM NPs would be a promising biomimetic nanodrug for chemo-gene combination therapy of MBC with high efficacy and safety in clinics.

Regarding the molecular mechanism, HIF1α overexpression could down-regulated TIMP1 and up-regulated MT6-MMP expression levels but not affected EMT markers expression. Our results suggested HIF1α might contribute to the invasion of pituitary null cell adenomas through activating HIF1α/TIMP1/MT6-MMP pathway but not EMT.

Phillygenin can enhance the immune response and inhibit angiogenesis in the TME in CRC by inhibiting HIF-1α. The online version contains supplementary material available at 10.1007/s10616-024-00679-2.

Knockdown of FUNDC1 using shRNA in HEC-1B and Ishikawa EC cells inhibited proliferation, migration and invasion, accompanied by enhanced chemotherapeutic susceptibility to carboplatin and paclitaxel. Accordingly, FUNDC1 could be a prospective prognostic biomarker and potential therapeutic target for EC.

Mechanistically, siTCTP inhibited VEGFR-2 tyrosine phosphorylation and phosphorylation of its downstream targets PI3K, Akt, and mTOR. Collectively, these findings indicate that TCTP can promote proliferation and angiogenesis via the VEGFR-2/PI3K and mTOR signaling pathways in ovarian tumor cells, providing new insight into the mechanism behind the involvement of TCTP in tumor angiogenesis.

Among these 24 targets, 10 hub-targets were identified (TLR4, ICAM1, TLR9, STAT3, TNFRSF1A, ERBB2, CXCR3, ACE, IKBKG and NOS2) which were significantly involved in GO processes such as positive regulation of DNA-binding transcription factor activity, peptidyl-tyrosine phosphorylation, positive regulation of inflammatory response, mononuclear cell proliferation, regulation of hemopoiesis and cytokine production involved in inflammatory response and KEGG pathways such as pathways in Tuberculosis, NF-kappa B signalling, HIF-1 signalling PD-L1 expression, and PD-1 checkpoint pathway in cancer. Molecular docking and dynamics simulations confirmed the stable interactions of imidazo[1,2-a]pyridine derivatives with core target active sites, highlighting their potential as novel anti-TB drug candidates.

HIF-1α/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.

We elucidate that an underappreciated function of truncated APC in CRC is its ability to drive an immunosuppressive program that boosts tumor progression. Our work could provide a new perspective for the clinical application of immunotherapy in patients with CRC resistant to ICB therapy.

PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.

The study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.

Understanding the regulatory network involving miR-210 under hypoxic conditions may reveal new therapeutic targets for combating PDAC and improving patient outcomes. Our data suggest that miR-210 is a critical regulator of HIF1-α expression, EMT, and the stemness of PDAC cells in hypoxic environments.

The present study demonstrated that YAP1 positively regulates aerobic glycolysis by inhibiting EGLN2 expression, which results in an increased HIF-1α protein level and transcriptional activity. YAP1 was positively regulated and significantly correlated with HIF-1α-targeted glycolytic genes, including glucose transporter type 1(GLUT1), hexokinase2 (HK2) and lactate dehydrogenase A (LDHA). Elevated YAP1 expression and concomitant downregulation of EGLN2 contributed to poor survival in patients with pancreatic cancer. Our results suggest that YAP1 may be a promising predictive marker and treatment target for human pancreatic cancer.

Casticin inhibits NSCLC cell proliferation by suppressing glycolytic reprogramming via HIF-1α regulation. These findings highlight the potential of casticin as an anticancer therapeutic, particularly in targeting glucose metabolism in NSCLC.

Mechanistically, the co-treatment with drugs-loaded Cs NPs was found to downregulate the expression of NOTCH-1 and HIF-1α, two key transcription factors involved in tumor cell survival and adaptation, suggesting that their inhibition is a crucial component of the therapeutic efficacy of this treatment strategy. Collectively, the findings of this study suggest that the co-delivery of Met and Dig via chitosan Cs NPs represents a promising therapeutic strategy for breast cancer, as it effectively targets key pathways involved in tumor growth and progression, and underscores the potential of Cs NPs as a versatile platform for cancer therapy.

Taken together, our data revealed for the first time that ailanthone regulated HIF-1α/LINC01956/FUS/β-catenin signaling pathway and thereby inhibited GBM progression.

Moreover, the O2-generating ability induced by Fc-SS-Fe/Cu could reverse the hypoxic tumor microenvironment, and importantly, the expression of PD-L1 on tumor cell surfaces could be effectively downregulated by inhibiting the HIF-1α pathways, thereby augmenting the effect of anti-PD-L1 (αPD-L1) therapy. Therefore, this study provides valuable strategies into enhancing PD-L1-mediated ICB therapy.

Notably, HIF-1α regulated the expression of cell cycle inhibitory proteins (p16, p21, p53) and senescence-associated secretory phenotype factors (IL-8, IL-6, CCL2), along with the expression of senescence-associated β-galactosidase, thereby exacerbating T-2 toxin-induced cellular senescence. These findings underscore the vital role of HIF-1α in T-2 toxin-induced senescence in SH-SY5Y cells.

Additionally, lower miR-128-3p levels existed in hypoxic GBM, leading to desensitizing temozolomide (TMZ)'s efficacy, a first-line therapeutic drug for GBM...Collectively, the HIF-1α/miR-128-3p/IL-8 signaling pathway plays a critical role in promoting the progression of hypoxic GBM. Targeting this signaling pathway holds promise as a potential therapeutic strategy.

Inhibition of piR-651 and piR-823 decreased the survival and metastasis of cancer cells, without causing vital structural changes in healthy cells. Future research in cancer gene therapy or genetic modification may benefit from investigating piR-651 and piR-823 as possible inhibitors of breast cancer invasion and metastasis.

In summary, high HIF-1α expression is potentially a baseline prognostic biomarker for poor RFS and cytarabine resistance in NPM1+FLT3-ITD- AML. Further studies with the large number of patients are warranted.

P=N/A, N=240, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

DAPK1 ablation in healthy donor hPASMCs leads to an increase in proliferation, while its overexpression provides the opposite effects. Together our data indicate that DAPK1 serves as a new inhibitor of the pro-proliferative and glycolytic phenotype of PH in PASMCs acting via HIF-signaling pathway.

Given the similarities between hepatic alveolar echinococcosis and liver cancer, current research is focused on treating the disease by targeting related signaling pathways using molecular drugs used for liver cancer. This article aims to summarize the biological regulation of HIF-1α and VEGFA overexpression in angiogenesis related to hepatic alveolar echinococcosis, as well as the impact of the BMP9-ID1 signaling pathway on the expression levels of HIF-1α and VEGFA, providing new insights for potential treatment strategies.

P=N/A, N=24, Recruiting, Queen Mary University of London | Not yet recruiting --> Recruiting | Trial completion date: Nov 2025 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Dec 2026

CT26 mouse model was established to assess the synergistic effect of silencing HIF-1α combined with oxaliplatin (OXA) and imiquimod (IMQ) on tumor growth. Compared with those in the control group, the expression levels of the anti-inflammatory cytokines IL-10 and IL-4 significantly decreased (P < 0.05). In conclusion, our findings suggest that inhibiting HIF-1α could serve as a rational strategy to enhance the antitumor response in the TME.

CT spectral quantitative parameters are significantly different among expression levels of immunohistochemical markers. The positive correlation between CT quantitative parameter and expression level of immunohistochemical markers suggests CT spectral imaging could predict biological characteristics of tumors.

Pan-cancer analysis found HIF1A expression was decreased in several tumors, and chemosensitivity analysis revealed that HIF1A was associated with sensitivity of several anti-tumor drugs, such as Sorafenib, Navitoclax, and Venetoclax. Our findings provide evidence for identifying high-risk population and facilitating individualized treatment in TCL patients with SE.

In the progression from CG to GPL, the HIF-1α pathway-mediated glycolysis was characterized by sequential activation, deactivation, and reactivation. SQQT attenuated glycolysis by targeting the HIF-1α pathway and improved abnormal cellular proliferation and apoptosis in the gastric mucosa, thereby exerting therapeutic effects on GPL.

Finally, we demonstrated the correlation and co-expression of LMP1-induced PARP1, HIF1A, HK2, and key glycolysis-related factors, further suggesting that LMP1 actively regulates the glycolysis pathway. Therefore, our study presents a comprehensive functional encyclopedia of the interactions between EBV antigens and host signaling pathways across various EBV-associated diseases, providing valuable insights for the development of therapeutic strategies.

These findings highlight the potential role of VEGF as a valuable prognostic marker in canine OSA, which could have potentially important implications for therapeutic targeting and clinical management of the disease. This study advances the understanding of angiogenesis in canine OSA, while emphasizing the need for continued research into the complex mechanisms regulating the interplay between hypoxia, angiogenesis and tumor progression.

The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept.

Additionally, FBP1 inhibited the proliferation, apoptosis, and invasion of thyroid cancer cells by modulating HIF-1α expression. Our results provide new insights into the role of FBP1 in PTC progression and indicate that targeting the FBP1-HIF-1α axis could be a promising therapeutic approach for this disease.

The expression of Hif1a, Nfkb, Tnfa, and Tgfb genes in the liver of LR animals was higher than in HR mice, which attested to more pronounced systemic inflammatory response. These data should be taken into account when developing new approaches for the treatment of neoplastic disorders.

Thus, we identified the VHL-HIF-1α/HIF-2α axis as an indispensable pathway that may be a novel target for mediating hepatic I/R injury.

CAR and CAR@BSANPs affect gene expression and may subsequently reduce the growth and proliferation of the MCF-7 cells. Molecular targeting of regulatory genes of the MCF-7 cells with CAR and CAR@BSANPs may be an effective therapeutic strategy against breast cancer.

HIF-1α is stabilized in keratinocytes in the presence of oxygen by high levels of HIF-1α transcripts, low levels of prolyl-4-hydroxylases (PHD2 and 3) and a low cellular α-ketoglutarate/lactate ratio, likely inhibiting PHD activity. Our data suggest a key role for constitutive HIF-1α expression allowing a Warburg-like metabolism in healthy, highly proliferative keratinocytes, similar to tumour cells.

The regulation of FGF21 influences glycolysis via the mTOR-HIF1α axis, highlighting its critical role in glucose metabolism and metabolic adaptation in response to energy availability.

Docking analysis revealed BPB may activate gene expression related to lipid metabolism and angiogenesis by interacting with PPARγ and hypoxia-inducible factor-1α (HIF-1α). This study illuminates BPB's potential role in advancing melanoma through lipid metabolism manipulation, highlighting the need for further research into the safety of BPA substitutes and their impact on cancer development.

Temozolomide (TMZ) represents the standard chemotherapy for GBM but has limited efficacy due to poor targeting and a hypoxic tumor microenvironment (TME)...An in vitro antitumor assay using spheroids showed that CCM-CeO2 reduced the IC50 value of TMZ from 174.5 to 42.6 μg/mL, likely due to the catalase-like activity of nanoceria. These results suggest that alleviating hypoxia and increasing ROS produced by chemotherapeutics could be an effective therapeutic strategy for treating GBM.