Esophageal cancer (ESCA) poses a significant challenge in oncology because of the limited treatment options and poor prognosis. Therefore, enhancing the therapeutic effects of radiotherapy for ESCA and identifying relevant therapeutic targets are crucial for improving both the survival rate and quality of life of patients.

To define the role of the transcription factor Snail family transcriptional repressor 1 (SNAI1) in ESCA, particularly its regulation of radiosensitivity.

A comprehensive analysis of TCGA data assessed SNAI1 expression in ESCA. Survival curves correlated SNAI1 levels with radiotherapy outcomes. Colony formation assays, flow cytometry, and a xenograft model were used to evaluate tumor radiosensitivity and apoptosis. Western blot validated protein expression, while Chromatin immunoprecipitation assays examined SNAI1's role in regulating epithelial-mesenchymal transition (EMT).

SNAI1 expression in ESCA cell lines and clinical specimens emphasizes its central role in this disease. Elevated SNAI1 expression is correlated with unfavorable outcomes in radiotherapy. Downregulation of SNAI1 enhances the sensitivity of ESCA cells to ionizing radiation (IR), resulting in remarkable tumor regression upon IR treatment in vivo. This study underscores the direct involvement of SNAI1 in the regulation of EMT, particularly under IR-induced conditions. Furthermore, inhibiting deacetylation effectively suppresses EMT, suggesting a potential avenue to enhance the response to radiotherapy in ESCA.

This study highlights SNAI1's role in ESCA radiosensitivity, offering prognostic insights and therapeutic strategies to enhance radiotherapy by targeting SNAI1 and modulating EMT processes.

Stem cell-based therapies hold significant potential for cancer treatment due to their unique properties, including migration toward tumor niche, secretion of bioactive molecules, and immunosuppression. Mesenchymal stem cells (MSCs) from adult tissues can inhibit tumor progression, angiogenesis, and apoptosis of cancer cells. We have previously reported the isolation and characterization of placenta-derived decidua basalis mesenchymal stem cells (DBMSCs), which demonstrated higher levels of pro-migratory and anti-apoptotic genes, indicating potential anti-cancer effects. In this study, we analyzed the anti-cancer effects of DBMSCs on human breast cancer cell lines MDA231 and MCF7, with MCF 10A used as control. We also investigated how these cancer cells lines affect the functional competence of DBMSCs. By co-culturing DBMSCs with cancer cells, we analyzed changes in functions of both cell types, as well as alterations in their genomic and proteomic profile. Our results showed that treatment with DBMSCs significantly reduced the functionality of MDA231 and MCF7 cells, while MCF 10A cells remained unaffected. DBMSC treatment decreased epithelial-to-mesenchymal transition (EMT)-related protein levels in MDA231 cells and modulated expression of other cancer-related genes in MDA231 and MCF7 cells. Although cancer cells reduced DBMSC proliferation, they increased their expression of anti-apoptotic genes. These findings suggest that DBMSCs can inhibit EMT-related proteins and reduce the invasive characteristics of MDA231 and MCF7 breast cancer cells, highlighting their potential as candidates for cell-based cancer therapies.

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.

Heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) is an RNA binding protein that is closely associated with the biological function and metabolism of RNA, which is involved in the malignant transformation of various tumor cells. However, the role and mechanisms of hnRNPAB in non-small cell lung cancer (NSCLC) are still unclear. In the present study, the expression levels of hnRNPAB in NSCLC and normal tissues were analyzed using the human protein atlas database and UALCAN database. The clinical significance of hnRNPAB was assayed using the data of NSCLC cases from The Cancer Genome Atlas database. Subsequently, two stable NSCLC cell lines with hnRNPAB knockdown were constructed and the effects of hnRNPAB silencing on cell viability, migration, invasion and epithelial-mesenchymal transition (EMT) were identified. Genes associated with hnRNPAB expression in NSCLC were screened using the Linked Omics database and verified by quantitative real-time PCR (RT-qPCR). The database analysis indicated that hnRNPAB was mainly expressed in the nucleus of NSCLC cells. Compared with the normal tissues, hnRNPAB expression was overexpressed in NSCLC tissues and was closely associated with the overall survival, sex, tumor-node-metastases classification, and poor prognosis of patients with lung adenocarcinoma. Functionally, knockdown of hnRNPAB inhibited the proliferation, migration, invasion and EMT of NSCLC cells and arrested the cell cycle at G1 phase. Mechanistically, the bioinformatics analysis and RT-qPCR verification demonstrated that hnRNPAB knockdown led to a significant expression change of genes associated with tumorigenesis. In conclusion, the present study indicated that hnRNPAB played an important role in the malignant transformation of NSCLC, supporting the significance of hnRNPAB as a novel potential therapeutic target for the early diagnosis and prognosis of NSCLC.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

As a devastating disease, breast cancer has been responsible for decrease in life expectancy of females and its morbidity and mortality are high. Breast cancer is the most common tumor in females and its treatment has been based on employment of surgical resection, chemotherapy and radiotherapy. The changes in biological behavior of breast tumor relies on genomic and epigenetic mutations and depletions as well as dysregulation of molecular mechanisms that autophagy is among them. Autophagy function can be oncogenic in increasing tumorigenesis, and when it has pro-death function, it causes reduction in viability of tumor cells. The carcinogenic function of autophagy in breast tumor is an impediment towards effective therapy of patients, as it can cause drug resistance and radio-resistance. The important hallmarks of breast tumor such as glucose metabolism, proliferation, apoptosis and metastasis can be regulated by autophagy. Oncogenic autophagy can inhibit apoptosis, while it promotes stemness of breast tumor. Moreover, autophagy demonstrates interaction with tumor microenvironment components such as macrophages and its level can be regulated by anti-tumor compounds in breast tumor therapy. The reasons of considering autophagy in breast cancer therapy is its pleiotropic function, dual role (pro-survival and pro-death) and crosstalk with important molecular mechanisms such as apoptosis. Moreover, current review provides a pre-clinical and clinical evaluation of autophagy in breast tumor.

It has been widely reported that glioma stem-like cells (GSCs) serve a crucial role in the malignant progression of glioma. In particular, recent studies have reported that long non-coding RNAs (lncRNAs) are closely associated with glioma development. However, the underlying molecular regulatory mechanistic role of GSCs remains poorly understood. The present study established two highly malignant glioma stem-like cell lines from clinical surgical specimens. In these, it was found that the lncRNA growth arrest-specific 5 (GAS5) expression was downregulated in GSCs and high-grade glioma tissues, compared with normal human astrocyte cells (NHAs) and normal brain tissues, respectively, which also showed a positive correlation with patient survival. Functional assays revealed that knocking down GAS5 expression promoted the proliferation, invasion, migration, stemness, and tumorigenicity of GSGs, while suppressing their apoptosis. Mechanistically, GAS5 directly sponged miR-23a, which in turn functioned as an oncogene by inhibiting E-cadherin, through the assays of reverse transcription-quantitative PCR (RT-qPCR) and luciferase reports. In addition, rescue experiments demonstrated that GAS5 could promote the expression and function of E-cadherin in a miR-23a-dependent manner. Collectively, these data suggest that GAS5 functions as a suppressor in GSCs by targeting the miR-23a/E-cadherin axis, which may be a promising therapeutic target against glioma.

Chemotherapy is a critical treatment for endocrine-related cancers; however, chemoresistance and disease recurrence remain a challenge. The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR). CAMs are cell surface molecules that facilitate cell-to-cell or cell-to-extracellular matrix binding. CAMs exert an adhesion effect and trigger intracellular signaling that regulates cancer cell stemness maintenance, survival, proliferation, metastasis, epithelial-mesenchymal transition, and drug resistance. To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers.

Background: Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. The application of advanced technology has promoted accurate diagnosis and treatment of cancer. Anhydroicaritin (AHI) is a flavonoid with therapeutic potential in BC treatment. The current study aimed to determine AHI's mechanism in BC treatment via RNA sequencing, comprehensive bioinformatics analysis, and experimental verification. Methods: Network pharmacology and MTT (3-(4,5)-dimethylthiazolyl-3,5- diphenyltetrazolium bromide) experiments were conducted to first confirm AHI's anti-BC effect. RNA sequencing was performed to identify the genes affected by AHI. Differential expression analysis, survival analysis, gene set enrichment analysis, and immune infiltration analysis were performed via bioinformatics analysis. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR) experiment, molecular docking, and drug affinity responsive target stability (DARTS) experiments were also performed to confirm AHI's direct effect on glutathione peroxidase 1 (GPX1) expression. Confocal immunofluorescence analysis was conducted to verify AHI's effect on the occurrence and development of epithelial-mesenchymal transition (EMT). Finally, BC nude mouse xenografts were established, and AHI's molecular mechanism on BC was explored. Results: Network pharmacology results demonstrated that AHI's therapeutic targets on BC were related to the proliferation, invasion, and metastasis of BC cells. AHI significantly inhibited the proliferation of 4T1 and MDA-MB-231 BC cells in the MTT experiments. RNA sequencing results showed that AHI upregulated the GPX1 expression in the 4T1 and MDA-MB-231 BC cells. Next, bioinformatics analysis revealed that GPX1 is less expressed in BC than in normal breast tissues. Patients with high GPX1 expression levels tended to have prolonged overall survival and disease-free survival than patients with low GPX1 expression levels in BC. Western blot and RT-PCR experiments revealed that AHI increased the protein and mRNA levels of GPX1. Molecular docking and DARTS experiments confirmed the direct binding combination between AHI and GPX1. After the evaluation of the EMT scores of 1,078 patients with BC, we found a potential anti-BC role of GPX1 possibly via suppression of the malignant EMT. The confocal immunofluorescence analysis showed that AHI increased E-cadherin expression levels and reduced vimentin expression levels in BC cells. Animal experiments showed that AHI significantly inhibited tumor growth. AHI also inhibited EMT by enhancing GPX1 and caspase3 cleavage, hence inhibiting EMT markers (i.e., N-cadherin and vimentin) and Ki-67. Conclusion: GPX1 plays a critical role in BC, which may be a biomarker for the prognosis. In addition, AHI suppressed EMT by increasing GPX1 expression, which may serve as a potential therapy for BC treatment.