MiR-34a reverses radiation resistance on ECA-109 cells by inhibiting PI3K/AKT/mTOR signal pathway through downregulating the expression of SIRT1

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

“…The mTOR signal pathway can be activated by various external factors such as growth factors, stress, oxygen, and amino acid, and is involved in many physiological processes, such as liposome synthesis, energy metabolism, and autophagy. The inducible knockout of mTOR in mouse airway epithelial cells and alveolar type II epithelial cells will exacerbate smoking-induced inflammation, autophagy, necrosis, and apoptosis, which will lead to airway inflammation and emphysema ( Liu et al, 2021 ; Wu et al, 2021 ; Ye et al, 2021 ). MircoRNA-mRNA regulatory network in Figure 3C demonstrated that KPNA6 and TOR1AIP2 were targeted by four miRNAs.…”

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

“…Class III SIRT1 Expression levels: functioning as a dual-role factor in HNSCC; SIRT1 expression significantly decreased in HNSCC according to TCGA database, however, SIRT1 expression was significantly lower in SCC-9 and SCC-25 [81] Cell proliferation: binding to the promoter of TGF-β, impeding CBP/p300-mediated acetylation, leading to transcriptional suppression, exerting inhibitory effects on the proliferation of OSCC [78] Invasion and metastases: inhibiting vimentin and N-cadherin expression, suppressing Smad2/3 phosphorylation and Smad4 deacetylation, impeding the EMT process in OSCC [82][83][84] Cell death: capsaicin hinders SIRT1 activity, augmenting acetylation of unc-51-like autophagy-activating kinase 1 and instigating autophagy in OSCC [90] Prognostic significance: potential as a valuable prognostic assessment tool according to Kaplan-Meier analysis and clinical observation [86] Therapy resistance: enhance cisplatin resistance of OSCC [88]; downregulation of SIRT1 resulted in PI3K/AKT/Mtor pathway inhibition, reversing the radio-resistance of ECA-109 cells [88]; SIRT1 inducing EBV-miR-BART4 mediated stemness and cisplatin resistance in NPC carcinoma side cells [89] SIRT2 Expression levels: TCGA, CPTAC and HPA databases showed decreased SIRT2 Mrna expression in HNSCC Prognostic significance: Kaplan-Meier survival analysis highlight the potential value of SIRT2 in validating prognosis…”

“…Lymph angiogenesis: playing an important role in HNSCC lymph angiogenesis [93] SIRT3 Expression levels: up-regulated expression in OSCC [94], however, enzyme deacetylation is reduced, indicating presence of variants such as p.Val208Ile [95] Cell proliferation: SIRT3 downregulation significantly restrains proliferation in ESCC [96] and OSCC [94] Invasion and metastases: mitigating augmented oxidative stress induced by miR-31, thereby promoting migration and invasion in OSCC [99,100] Cell death: participating in redox homeostasis, energy metabolism and mitochondrial fission, inducing intrinsic apoptosis [94] Therapy resistance: SIRT3 downregulation heightens OSCC cell sensitivity to radiation and cisplatin treatments [101] SIRT4 Expression levels: down-regulated expression in HNSCC according to TCGA Invasion and metastases: SIRT4 downregulation associated with a more aggressive tumor phenotype and unfavorable prognosis [104] SIRT5 Cell proliferation and metastasis: inhibiting Warburg effect, countering ROS damage and inhibiting cell proliferation and metastasis [88] Therapy resistance: SIRT5 exhibit carcinogenic characteristics, leading to chemotherapy and radiotherapy resistance [88] SIRT6 Expression levels: genetic expression profiling of 34 HNSCC patients [107], OSCC tissues [108] and TCGA database both revealed a significant upregulation of SIRT6 in cancer group; however, 82 cases of OLP and 77 cases of OSCC were examined, revealing significantly lower expression of SIRT6 in OSCC lesions [108] Pro-differentiation: down-regulation of SIRT6 replicates the pro-differentiation effects of miR-34a in SCCs [109] Cell death: increasing ROS expression, promote apoptosis, modulate telomere maintenance in OSCC [88] Prognostic significance: associated with shorter overall survival [28] SIRT7 Invasion and metastases: inhibiting EMT, invasion, migration and metastasis in OSCC cells [112]; miR-770 facilitating migration and invasion of OSCC cells through the activation of SIRT7/Smad4 pathway [113]; SIRT7 expression positive associated with stromal lymphocytic infiltration and invasion depth in OSCC [108] Class IV HDAC11 Expression levels: TCGA database showed a decreasing trend of HDAC11 expression in HNSCC samples (SMRT/NcoR) complex, activating deacetylase activity of HDAC1-3 and facilitating transcriptional silencing at specific loci through interactions with regulatory proteins. HDAC8, on the other hand, exhibits substantial histone deacetylase activity, suggesting a potential capacity for independent functionin...…”

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

“…In vitro and in vivo experiments showed that inhibition of the PI3K/AKT/mTOR signaling pathway by UHRF1 knockdown inhibited ESCC cell growth and enhanced tumor radiosensitivity, and shUHRF1 binding to radiation significantly increased ESCC cell apoptosis [ 132 ]. Similar to UHRF1, miR-34a [ 133 ] and miR-519 [ 134 ] reversed radioresistance in ESCC cells by inhibiting the PI3K/AKT/mTOR signaling pathway. Treatment with the mTOR inhibitor temsirolimus significantly inhibited the activation of mTOR effectors and reduced ESCC cell proliferation [ 135 ]; everolimus significantly inhibited angiotensin II-induced ESCC cell proliferation [ 136 ].…”