Molecular Carcinogenesis最新文献

Gallbladder cancer (GBC) is a rare but aggressive malignancy, often diagnosed at advanced stages due to its asymptomatic progression and lack of reliable biomarkers. Chronic inflammation plays a crucial role in its pathogenesis, with inflammatory pathways contributing to tumor development. This study evaluates the diagnostic potential of microRNA19a and microRNA146a, key regulators of inflammatory and oncogenic pathways, in distinguishing GBC from cholelithiasis and healthy controls. An observational analytical study was conducted on 60 participants, divided into three groups: GBC (n = 20), cholelithiasis (n = 20), and non-dysplastic/healthy controls (n = 20). microRNA expression levels in tissue and plasma samples were quantified using RT-PCR and qPCR, with ΔCq values normalized to U6 RNA. Receiver Operating Characteristic (ROC) analysis assessed diagnostic performance, and correlations between tissue and plasma expression levels were examined. Most GBC cases (65%) were diagnosed at Stage IV, with 75% showing liver infiltration. microRNA19a and microRNA146a expression levels were significantly elevated in GBC tissues compared to the other groups (p < 0.0001). Plasma microRNA146a demonstrated high diagnostic accuracy, with an AUC of 0.953, sensitivity of 80%, and specificity of 95%, outperforming microRNA19a (AUC 0.388, sensitivity 20%, specificity 95%). Strong positive correlations between tissue and plasma expression were observed for microRNA146a (r = 0.693, p = 0.0007) and microRNA19a (r = 0.564, p = 0.010), supporting their potential as circulating biomarkers. microRNA146a exhibits good diagnostic utility in differentiating GBC, particularly in advanced disease stages, while microRNA19a reflects inflammation-driven carcinogenesis. Plasma-based microRNA detection offers a promising noninvasive diagnostic approach for early and accurate GBC detection. Further large-scale studies are warranted to validate these biomarkers and explore their therapeutic implications.

RNF7 (Ring Finger Protein 7) is a key component of CRLs (Cullin-RING-type E3 ubiquitin ligases) and has been found to possess intrinsic anti-ROS capabilities. Aberrant expression of RNF7 has been observed in various tumor types and is known to significantly influence tumor initiation and progression. However, the specific role of RNF7 in glioblastoma remains unclear. IDH (isocitrate dehydrogenase) mutations, which induce metabolic reprogramming and result in notable heterogeneity among glioma with different IDH genotypes. Through analysis of public glioma databases, we identified a high expression of RNF7 in glioma and its correlation with patient prognosis. Moreover, we observed variations in RNF7 expression and its association with patient outcomes under different treatment modalities among different IDH genotypes. In this study, we demonstrated the critical role of RNF7 in the malignant phenotype of IDH1-mutant glioma and its contribution to radiation resistance. Subsequent functional enrichment analysis of RNF7 in glioma, coupled with validation through cellular experiments, confirmed its significant involvement in maintaining redox balance. Our findings suggest that RNF7 exerts a buffering effect against radiation-induced oxidative stress and counterbalances the redox stress induced by IDH1 mutation through its anti-ROS activity. Additionally, our follow-up investigations revealed that the upregulation of RNF7 after radiation exposure and in IDH1-mutant glioma cells is induced by ROS. Collectively, our study underscores the potential of RNF7 as a molecular biomarker in glioma. Elevated RNF7 expression often indicates a heightened metabolic resilience in glioma, leading to resistance against radiotherapy.

Vacuolar protein sorting 45 (VPS45) has recently been implicated in the development of ovarian cancer and non-small cell lung cancer. However, its role in the onset and progression of hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of VPS45 in HCC. Bioassays were conducted to assess the prognostic significance of VPS45 in HCC. Techniques such as western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm the expression levels of VPS45 in HCC tissues and cell lines, as well as to evaluate the expression of downstream effectors in its potential tumorigenic pathways. The impact of VPS45 on HCC cell invasion, proliferation, and migration was assessed using the Cell Counting Kit-8 (CCK-8), wound healing, and transwell assays. Furthermore, the effect of VPS45 on HCC tumorigenesis in vivo was evaluated through subcutaneous tumor formation assays in BALB/c nude mice. VPS45 is markedly overexpressed in both HCC tissues and cell lines. Its expression escalates with advancing tumor grade and clinical stage, and high VPS45 levels are indicative of poor prognosis. In vitro experiments revealed that VPS45 overexpression significantly boosts HCC cell proliferation, migration, and invasion. Conversely, VPS45 knockdown hindered HCC progression in vivo. Investigation into pathway protein expression suggests that VPS45 facilitates HCC progression through its involvement in the Wnt/β-catenin signaling pathway. The overexpression of VPS45 contributes to the development of malignant phenotypes in HCC cells, resulting in a poor prognosis. Targeting VPS45 may offer a viable therapeutic strategy for managing HCC.

Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.

Hepatocellular carcinoma (HCC) is a major global health concern that accounts for more than 80% of all primary hepatic carcinomas. The long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been linked to HCC cell stemness and proliferation. However, the exact function of FGD5-AS1 in HCC remains unclear. Cell viability and proliferation were examined using the CCK8 and colony formation assays, respectively. Cell stemness was examined using a sphere formation assay. To investigate the relation between Musashi 2 (MSI2) and FGD5-AS1 (or protein kinase D1 [PKD1]), RNA immunoprecipitation and RNA pull-down assays were used. Furthermore, a xenograft mouse model was established to evaluate the function of FGD5-AS1 in vivo. FGD5-AS1, MSI2, and PKD1 were upregulated in the HCC tissues. FGD5-AS1 knockdown significantly inhibited the viability, proliferation, and stemness of HCC cells and decreased the expression of MSI2, PKD1, octamer-binding transcription factor 4, SOX2, NANOG, and Prominin-1 in HCC cells. Mechanistically, FGD5-AS1 increased PKD1 mRNA stability by upregulating MSI2 expression. Both MSI2 and PKD1 ameliorated sh-FGD5-AS1's inhibition of HCC cell viability, proliferation, and stemness. Furthermore, FGD5-AS1 silencing inhibited HCC tumor growth and stemness in vivo. FGD5-AS1 promotes the stemness of HCC cells by activating the MSI2/PKD1 axis. Our study provides a new theoretical foundation for the development of novel HCC treatments.

β-elemene has a variety of anti-inflammatory, antioxidant, and antitumor effects. Currently, the influence of β-elemene on adrenocortical carcinoma (ACC) malignant progression and action mechanism remains unclear. This research aims to explore the influence and action mechanism of β-elemene on ACC progression. The impacts of β-elemene on ACC cell viability, proliferation, migration, and apoptosis were investigated through CCK-8 assay, clone formation assay, Transwell experiment, Wound healing assay, and flow cytometry. The miR-486-3p expression was analyzed utilizing RT-qPCR. According to different databases, neuronal pentraxin 1 (NPTX1) is the predicted downstream target gene of miR-486-3p. Western blot and RT-qPCR were utilized to examine NPTX1 expression. Silencing miR-486-3p or Overexpression NPTX1 in ACC cells further explored whether β-elemene affects ACC cells by regulating miR-486-3p/NPTX1. Finally, a subcutaneous graft tumor model was constructed to investigate how β-elemene may impact tumor growth in vivo. β-elemene decreased the cell viability, hindered cell proliferation and migration capacity, and induced apoptosis of ACC cells. miR-486-3p level in ACC cells was notably reduced in comparison to normal cells, but treatment with β-elemene markedly increased miR-486-3p expression. Additionally, ACC cells showed high level of NPTX1, while miR-486-3p targeted negative regulation of NPTX1. Overexpression miR-486-3p hindered the malignant progression of ACC cells, whereas overexpression NPTX1 reversed the impact of overexpression miR-486-3p. Silencing miR-486-3p or overexpression NPTX1 both attenuated the suppressive influence of β-elemene on the malignant behavior of ACC cells. Additionally, tumor growth was suppressed and apoptosis was induced in tumor cells in vivo by β-elemene. In conclusion, β-elemene reduces ACC cell viability, hinders proliferation and migration, and induces apoptosis through the miR-486-3p/NPTX1 axis.

Thoracic tumours represent a significant proportion of malignant cancers. While radiotherapy (RT) improves prognosis, it can also lead to side effects such as radiation-induced pneumonitis (RP). Since SIRT6 is involved in DNA repair, energy metabolism and inflammation, this study aims to investigate the expression of SIRT6 in lymphocytes as a potential biomarker and therapeutic target for RP. This study included 170 patients diagnosed with thoracic tumours, all of whom underwent thoracic RT. RP was evaluated and classified as severe RP (SRP) and lower as non-severe RP (NSRP). Analyses were performed using SPSS version 26.0 and the R. Among 170 patients in this study, 124 developed NSRP, and 46 experienced SRP. The univariate analysis showed that SIRT6 expression (cOR, 0.33, 95%CI, 0.18-0.97 before RT and 0.31, 0.19-0.98 after RT), clinical factors, dosimetric parameters and haematological/serological parameters were associated with SRP before and after RT. Our multivariable logistic regression showed that SIRT6 expression was significantly associated with risk of SRP before (aOR, 0.32, 95%CI, 0.15-0.96) and after RT (aOR, 0.32, 95%CI, 0.18-0.99) after adjustment with other confounders. Moreover, the receiver operating characteristic curve analysis revealed that the combined multivariable model exhibited superior predictive capability compared to any single predictor (overall AUC, 0.93, 95%CI, 0.90-0.97 before RT and AUC, 0.91, 95%CI, 0.87-0.96 after RT). The expression of SIRT6 alone or in combination with other risk factors was associated with an increased risk of SRP, suggesting a novel approach for the prevention and treatment of radiation pneumonitis in clinical practice.

Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor-positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c-Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c-Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR-141/200a. Additionally, HGF/c-Met activated NF-κB, forming a positive feedback loop of EZH2/HOTAIR-miR-141/200a-HGF/c-Met-NF-κB. Our findings indicated that HGF/c-Met functioned as an important biomarker for TR, and HGF/c-Met inhibition provided a novel approach to TR treatment.

Esophageal squamous cell carcinoma (ESCC) is prone to metastasis and is a leading cause of mortality. The cytoskeleton is closely related to cell morphology and movement; however, little research has been conducted on ESCC metastasis. In this study, we found that the anchoring filament protein ladinin 1 (LAD1) specifically binds to LINC01305 for co-regulating the level of modulating cortactin proteins (CTTN) and neuronal Wiskott-Aldrich syndrome protein (N-WASP) phosphorylation, which mediates cytoskeletal reorganization and affects the metastasis of ESCC cells. Additionally, LINC01305 and LAD1 jointly promoted the epithelial-mesenchymal transition (EMT) process by activating the phosphoinositide-3-kinase-protein kinase B (PI3K/AKT) signaling pathway. Moreover, LINC01305 and LAD1 were related to the late clinical stage and lymph node metastasis of ESCC. Our study demonstrated that LINC01305 and LAD1 are major determinants of ESCC dissemination and revealed a novel molecular mechanism of cytoskeletal reorganization that controls ESCC metastasis. Trial Registration: N/A.