MicroRNA-124 conducts neuroprotective effect via inhibiting AK4/ATF3 after subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124.

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

Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half of them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote the release of cytokines and chemokines, and triggers inflammatory reactions and changes in the tumor microenvironment (TME), thereby inhibiting the immune function and causing the invasion and metastasis of ESCC. Radioresistance is the major cause of disease progression and mortality in cancer, and it is associated with heterogeneity. Therefore, a better understanding of the radioresistance mechanisms may generate more reversal strategies to improve the cure rates and survival periods of ESCC patients. We mainly summarized the possible mechanisms of radioresistance in order to reveal new targets for ESCC therapy. Then we summarized and compared the current strategies to reverse radioresistance.

Emerging role of cancer-associated fibroblasts in esophageal squamous cell carcinoma.

Esophageal carcinoma is the sixth leading cause of cancer death globally and the majority of global cases are esophageal squamous cell carcinoma (ESCC). Difficulty in diagnosis exists as more than 70% of ESCC patients are diagnosed at the intermediate or advanced stage. Cancer-associated fibroblasts (CAFs) have been considered one of the crucial components in the process of tumor growth, promoting communications between cancer cells and the tumor microenvironment (TME). CAFs grow alongside malignancies dynamically and interact with ESCC cells to promote their progression, proliferation, invasion, tumor escape, chemo- and radio-resistance, etc. It is believed that CAFs qualify as a promising direction for treatment. Analyzing CAFs' subtypes and functions will elucidate the involvement of CAFs in ESCC and aid in therapeutics. This review summarizes current information on CAFs in ESCC and focuses on the latest interaction between CAFs and ESCC cancer cell discoveries. The origin of CAFs and their communication with ESCC cells and TME are also demonstrated. On the foundation of a thorough analysis, we highlight the clinical prospects and CAFs-related therapies in ESCC in the future.

Inhibitory receptors and checkpoints on NK cells: Implications for cancer immunotherapy.

With the success of immunosuppressive checkpoint in tumor therapy, the corresponding adverse response and drug resistance defects have been exposed. T cells and NK cells are the body's immune system of the two substantial main forces. in recent years, study of T cell checkpoints appeared a certain block, such as PD-1 the effect not benign, on the distribution of NK cell surface excitatory and inhibitory receptors under normal conditions to maintain steady, could be targeted in the tumor treatment blockade have therapeutic effect. This paper reviews the function of NK cells and the effects of corresponding receptors in various types of tumors, providing a direction for the selection of appropriate gate control sites for future treatment.

Role of O-GlcNAcylation in cancer biology.

One of the general characteristics of cancer cells is the abnormal increase of O-GlcNAcylation. Recent studies have shown that it affects the basic functions of proteins and regulates multiple phenotypes of cancer cells through key signals and metabolic pathways. O-GlcNAcylation is a covalent linkage between the ß-D-N-acetylglucosamine (GlcNAc) sugar and target protein. It interacts with many other types of post-translational modifications and works together in the whole process of cancer development. For example, it regulates cell activities such as cell signal transduction, transcription, cell division, metabolism and cytoskeleton regulation. In this review, we summarized the general concept of O-GlcNAcylation and its related role in the ten major tumor phenotypes.

TESC acts as a prognostic factor and promotes epithelial-mesenchymal transition progression in esophageal squamous carcinoma.

BACKGROUND: Tescalcin (TESC) is a critical regulator of cell differentiation and growth, promoting malignant progression in various tumors. However, the role of TESC in esophageal squamous carcinoma (ESCC) remains unclear. METHODS: Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were utilized to identify the difference in TESC expression between ESCC tissues and normal tissues adjacent to the carcinoma. The relationship between TESC and several clinicopathological features was shown by the chi-square test. Log-rank analysis and Cox regression were used to detect the relationship between TESC and the prognosis in ESCC. Clone formation and cell count kit-8 (CCK-8) were applied to detect the impact of TESC on ESCC proliferation. Wound healing assay and transwell assay were used to confirm the influence of TESC on the invasion and migration. Spearman correlation coefficient was used to describe the correlation between TESC and epithelial-mesenchymal transition (EMT)-related protein expression in ESCC. Western blot was used to detect the effect of TESC on the expression of E-cadherin, N-cadherin, and Vimentin as well as AKT signaling pathway. Xenograft tumors were developed to test the pro-tumorigenic impacts of TESC in vivo. RESULTS: TESC was upregulated expression in ESCC tissues and was linked to poorer prognosis and worse tumor infiltration, TNM stage, and lymph node metastasis. Meanwhile, TESC was able to act as an independent prognostic factor in ESCC. TESC promoted tumor cell proliferation, invasion, migration, EMT progression, and activated the phosphorylation of the AKT pathway. Furthermore, TESC knockdown inhibited the growth of carcinoma in vivo. CONCLUSION: TESC is a predictive factor for poor prognosis in ESCC and may provide a new strategy for ESCC treatment.

Cancer stem cells and angiogenesis.

Cancer remains the primary cause of mortality in developed nations. Although localized tumors can be effectively addressed through surgery, radiotherapy, and other targeted methods, drug efficacy often wanes in the context of metastatic diseases. As a result, significant efforts are being made to develop drugs capable of not only inhibiting tumor growth but also impeding the metastasis of malignant tumors, with a focus on hindering their migration to adjacent organs. Cancer stem cells metastasize via blood and lymphatic vessels, exhibiting a high mutation rate, significant variability, and a predisposition to drug resistance. In contrast, endothelial cells, being less prone to mutation, are less likely to give rise to drug-resistant clones. Furthermore, the direct contact of circulating anti-angiogenic drugs with vascular endothelial cells expedites their therapeutic impact. Hence, anti-angiogenesis targeted therapy assumes a pivotal role in cancer treatment. This paper provides a succinct overview of the molecular mechanisms governing the interaction between cancer stem cells and angiogenesis.

OTX1 regulates tumorigenesis and metastasis in glioma.

The most prevalent kind of primary brain tumors, gliomas, have a dismal prognosis. Recent advances in the tumor-promoting ability of OTX1 have drawn increasing attention. The overexpression of OTX1 has been reported to be associated with tumor-promoting effects in several malignancies, but its expression in gliomas is unknown. The oncogene OTX1 is increased in gliomas and is linked to a poor prognosis, as we show here. The degree of OTX1 positive expression is doubtlessly concomitant with the grade of glioma. We observed that OTX1 was up-regulated in gliomas, influenced the epithelial-mesenchymal transition (EMT), encouraged glioma cell growth and proliferation, and was linked to a poor clinical outcome for patients. At present, the prognosis of glioma is still not optimistic, and further research is needed to find a new target for treatment. According to our research, OTX1 is anticipated to emerge as a novel biological target for determining glioma prognosis and treatment.

A patient with BRAF N581S mutation-positive lung adenocarcinoma demonstrates durable response to combined anlotinib and tislelizumab: A case report and literature review.

BACKGROUND: Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with BRAF V600E mutation-positive NSCLC. Nevertheless, the treatment strategy for NSCLC patients with BRAF non-V600E mutations remains limited. CASE PRESENTATION: Here, we present a NSCLC patient with a BRAF N581S mutation, which is a class III BRAF mutation, and this patient had a durable response to targeted therapy with combined anlotinib and tislelizumab. CONCLUSION: We hope to bring more attention to rare non-V600 BRAF mutations by presenting this case of NSCLC.

Myeloid-derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in cancer.

Myeloid-derived suppressor cell (MDSC) mainly exists in tumor microenvironment (TME) and interferes with normal immune response of the body. These immature differentiated cells cooperate with tumor cells for immune escape and proliferation. The subtypes of MDSC are different in different organisms, and STAT become a high priority for the signaling pathway mediating the regulation of MDSC. The surface of MDSC cell population contains a variety of signal molecular receptors, and its differentiation degree is toilless to be chemotaxis by different factors. The role of MDSC in silencing T cells and promoting regulatory T cells (Treg) is particularly significant. This review mainly contains the origin of MDSC, the characteristics of subgroups, the focus of the study on MDSC heat molecules and signaling pathways, the relationship between MDSC and carcinoma, prognosis and hope to propose an overview of current MDSCs- targeting therapies so as to provide new ideas for cancer treatment.

Tumor-associated macrophages: Potential therapeutic targets and diagnostic markers in cancer.

Macrophages are plastic and functionally diverse, present in all tissues, and play a key role in organisms from development, homeostasis and repair, to immune responses to pathogens. They are central to many disease states and have emerged as important therapeutic targets for many diseases. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are key factors influencing cancer progression, metastasis and tumor recurrence. TAMs can be derived from different sources and exert different pro- or anti-tumor effects based on the type, stage and immune composition of the tumor. TAMs are highly heterogeneous and diverse, and have multiple functional phenotypes. There is still a great deal of controversy regarding the relationship between TAMs and prognosis of cancer patients. In this review, we summarize the characteristics of common markers of TAMs as well as explore the prognostic role of TAMs in different cancers including lung, breast, gastric, colorectal, esophageal and ovarian cancers.

RUNX1 predicts poor prognosis and correlates with tumor progression in clear cell renal carcinoma.

BACKGROUND: Runt-related transcription factor 1 (RUNX1), also called acute myeloid leukaemia 1, is a member of RUNX family of transcription factors. This family is composed of evolutionarily conserved transcription factors that function as critical lineage determinants in various tissues, however its function in cancer development and clinical significance in RCC are still unknown. METHODS: We used paraffin-embedded tumor tissues from 100 patients and fresh-harvested and paired adjacent normal renal tissues from 15 RCC patients who underwent primary surgical resection in Xijing Hospital between 2018 and 2022. The expression level of RUNX1 was evaluated by immunohistochemistry and Western Blot. RUNX1 promoted tumor cells proliferation, migration and invasion were verified by CCK-8, wound-healing and transwell assays. Finally, we constructed a xenografts model of the 786-O cell lines to observe the effect of RUNX1 on tumorigenesis in vivo. RESULTS: TCGA database showed higher RUNX1 expression levels in KIRC (kidney renal clear cell carcinoma). In overall survival analysis, RCC patients with higher RUNX1 expression level would have a shorter survival period than those with lower expression. Similarly, immunohistochemical results of our cohort also showed that RUNX1 was over-expression in cancer tissues than in corresponding non-cancer tissues. We also proved this result at protein level by western-blot. Meanwhile, prognostic and OS analyses of our cohort showed that the RUNX1 expression level was an individual prognostic factor in RCC patients. CCK-8, wound-healing and transwell assays proved that the overexpression of RUNX1 in Caki-1 cells promoted the proliferation, migration and invasion of the cells. Knocking down RUNX1 in 786-O cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of RUNX1 in 786-O cells slowed down the growth of tumor. CONCLUSION: RUNX1 is a poor prognostic factor of clear cell renal carcinoma, which may provide a novel therapeutic target for ccRCC.

INHBB promotes tumor aggressiveness and stemness of glioblastoma via activating EGFR signaling.

BACKGROUND: As most common primary tumor in adult's brain, the glioblastoma (GBM) still ends up with poor survival period. Little progress has been made in recent decades in terms of improving prognosis. There's still an urgent need for novel targets and strategies to overcome such malignancy. METHODS: Both the Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze expression differences and correlations. The immunohistochemistry and survival analysis were used to verify expression differences. Tumorigenesis was assessed using cholecystokinin and the orthotopic xenograft model. Metastasis was determined by the transwell assay and the tail vein xenograft model. RESULTS: Inhibin subunit beta B (INHBB) was upregulated in GBM and predicted poor survival. It promoted tumor growth, invasion and stemness in GBM. INHBB expression correlated with the epidermal growth factor receptor (EGFR) expression and downstream AKT and ERK expression levels. The increased tumor progression induced by INHBB could be inhibited by afatinib. CONCLUSION: This study revealed INHBB as a tumor progression and independent prognostic factor in GBM, which could be a potential upper stream molecular of EGFR/ERK/AKT signaling.

TRIM21 promotes tumor progression and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: The ubiquitin ligase family member triplex motif protein 21 (TRIM21), which is involved in the proliferation, metastasis, and selective death of tumor cells, is crucial in the ubiquitination of a number of tumor marker proteins. As research progresses, more studies demonstrate that TRIM21 expression levels can be used to predict cancer prognosis. However, it is unclear how exactly TRIM21 contributes to cervical squamous carcinoma. METHODS: Immunohistochemistry, Western Blot, and q-PCR were utilized to determine the expression level of TRIM21 in 113 patients with CESC removed by stage I surgery at Xijing Hospital from 2018 to 2023 using paraffin-embedded tumor tissues and 12 pairs of fresh tumor tissues and their paracancerous tissues. Log-rank analysis using SPSS 23.0 was performed for prognosis and survival analysis using univariate/multifactorial analysis. CCK-8, wound-healing and Scratch assay verified that TRIM21 promoted cell proliferation, migration and invasion. The effect of overexpression and knockdown of TRIM21 on tumor stemness was examined using sphere-forming assay and Western Blot. Finally, we constructed a xenograft model to observe the effect of TRIM21 on tumorigenesis in Si Ha cell lines in vivo. RESULTS: TRIM21 expression is greater in CESC tissues than in paracancerous tissues, according to immunohistochemical data. Similarly, at the protein and mRNA levels, we verified this conclusion using Western-Blotting and q-PCR. Prognostic and OS analysis showed that TRIM21 expression levels are associated with individual prognostic factors. CCK-8, Wound healing, Transwell, and Sphere-forming tests all demonstrated that TRIM21 overexpression enhances Ca Ski cell proliferation, migration, invasion, and stemness. TRIM21 knockdown in Si Ha inhibited tumor cell proliferation, migration, invasion, and stemness. The experimental results of xenograft models demonstrated that TRIM21 knockdown in Si Ha cells inhibited tumor development. CONCLUSION: TRIM21 is a poor predictor of prognosis for cervical squamous cell carcinoma and might open up new avenues for investigation into therapeutic targets.

FAM107A as a tumor suppressor in esophageal squamous carcinoma inhibits growth and metastasis.

BACKGROUND: Sequence similarity Family 107 member A (FAM107A) has been recognized as a tumor suppressor of various malignancies, which suppresses tumor proliferation and metastasis. Its specific role in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: Public datasets including Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO), quantitative real-time PCR (qRT-PCR), and Western blot were utilized for comparative analysis of FAM107A expression between ESCC and normal tissues. The link between FAM107A and clinicopathological features, as well as prognosis determined through χ2-test, log-rank analysis, and univariate and multivariate analyses, respectively. The impact of FAM107A on ESCC cell malignant behavior was confirmed through in vitro assays, including cell counting using the Cell Counting Kit-8 (CCK-8), clonal formation, wound healing, and transwell assays. Western blot analysis was employed to assess the effects of FAM107A on tumor epithelial-mesenchymal transition (EMT) and cell cycle-related proteins. Finally, xenograft tumors were developed to investigate the influence of FAM107A on ESCC growth in vivo. RESULTS: FAM107A exhibited low expression in ESCC tissues. Reduced FAM107A expression was associated with a poorer prognosis and unfavorable clinicopathological characteristics, such as degree of differentiation, T-stage, and N-stage. Overexpression of FAM107A suppressed ESCC cell proliferation, invasion, migration, the EMT process, and cell cycle progression. Finally, FAM107A overexpression inhibited tumor development in vivo. CONCLUSION: The decreased expression of FAM107A is indicative of a worse prognosis for ESCC patients. FAM107A exerts inhibitory impacts on malignant behavior and may hold promise as a therapeutic target for ESCC.

High PGAP3 expression is associated with lymph node metastasis and low CD8+T cell in patients with HER2+ breast cancer.

BACKGROUND: Breast cancer (BC) stands as the most prevalent malignancy among women and ranks as the second most frequently diagnosed cancer globally among newly identified cases. Post-GPI attachment to proteins factor 3（PGAP3）was reported to involve in lipid remodeling. However, its specific role in breast cancer remains inadequately elucidated. Consequently, the principal objective of this study was to investigate the clinical significance of PGAP3 in breast cancer. METHODS: We conducted an extensive analysis using both public databases and our own sample cohort to assess the role of PGAP3 in breast cancer. Immunohistochemistry was employed to assess PGAP3 expression, immune markers, and the co-expression of PGAP3 with key susceptibility genes. Data analysis was performed using the R programming language. RESULTS: Our findings revealed that PGAP3 is significantly overexpressed in breast cancer, particularly in human epidermal growth factor 2 positive (HER2 +) breast cancer cases (p < 0.001). Co-expression analyses demonstrated a significant correlation between PGAP3 and susceptibility genes associated with breast cancer, including BRCA1, BRCA2, PALB2, ATM, CHEK2, RAD51C, and RAD51D (p < 0.05). Logistic regression analysis identified PGAP3 as a significant predictor of estrogen receptor (ER), progesterone receptor (PR), HER2, and lymph node metastasis status (p < 0.01). Furthermore, higher PGAP3 expression was associated with decreased infiltration of CD8 + T cells in breast cancer samples. CONCLUSION: Our study sheds light on the clinical significance of PGAP3 in breast cancer. PGAP3 is not only overexpressed in breast cancer but also correlates with key susceptibility genes, lymph node metastasis, and CD8 + T cell infiltration. These findings provide valuable insights into the potential role of PGAP3 as a biomarker in breast cancer and may contribute to our understanding of the disease's pathogenesis.

MUC1 promotes cancer stemness and predicts poor prognosis in osteosarcoma.

Osteosarcoma (OS) is one of the most common primary bone malignancy. Combining chemotherapy and surgical treatment significantly improved clinical outcomes for osteosarcoma patients. Osteosarcoma stem cells (OSCs) are often more malignant than differentiated cancer cells and are a key determinant of responses to chemotherapy and radiation therapy, therefore, the removal of OSCs could be an effective therapeutic strategy. Myxoprotein 1 (MUC1) is aberrantly overexpressed in many human cancers and it promotes cancer stemness through activation of pluripotency networks. In this study, we observed elevated MUC1 in osteosarcoma and a depressed prognosis in patients with high MUC1 expression profiles. Our observations also revealed that MUC1 promoted OS stemness and tumor metastasis both in vivo and in vitro. These data led us to hypothesize that MUC1 may be a therapeutic target for patients with OS.

MAPK9 is Correlated with a Poor Prognosis and Tumor Progression in Glioma.

BACKGROUND: Glioma has a high incidence in young and middle-aged adults and a poor prognosis. Because of late diagnosis and uncontrollable recurrence of the primary tumor after failure of existing treatments, glioma patients tend to have a poor prognosis. Recent advances in research have revealed that gliomas exhibit unique genetic features. Mitogen-activated protein kinase 9 (MAPK9) is significantly upregulated in mesenchymal glioma spheres and may be a new target for glioma diagnosis. This study aimed to investigate the potential diagnostic significance and predictive value of MAPK9 in glioma. METHODS: Paraffin-embedded tumor tissues and paracancerous tissues were collected from 150 glioma patients seen at the General Hospital of Northern Theater Command. Immunohistochemistry and western blot assays were used to detect the expression levels of MAPK9. Prognosis and survival analyses were performed using SPSS 26 software for univariate/multivariate analysis and log-rank analysis. Cellular models were used to assess the effect of MAPK9 overexpression and knockdown in vitro. RESULTS: MAPK9 expression was higher in glioma tissues than in paraneoplastic tissues. Prognostic and survival analyses revealed that the MAPK9 expression level is an independent prognostic factor in glioma patients. In addition, overexpression of MAPK9 significantly promoted the proliferation and migration of primary glioma cells, possibly via the Wnt/ß-catenin-regulated EMT pathway. CONCLUSIONS: MAPK9 is an independent prognostic factor in glioma and is involved in tumor progression.

Ferroptosis in cancer stem cells.

Ferroptosis is an iron-dependent form of RCD correlates with the accumulation of markers of lipid peroxidation. Bulks of studies focusing on revealing ferroptosis and its regulators involved in oncogenic pathways. Connection between iron metabolism and abnormal iron metabolism in CSCs synergistically making ferroptosis a target process of great potential in combating with CSCs to improve therapeutic effectiveness and reverse resistance. Ferroptosis inducers could specifically induce CSCs death in tumors, predisposing ferroptosis to a target in killing CSCs to overcome cancer resistances. By ferroptosis induction and other cell death pathways in CSCs, cancer therapeutic outcome would be improved.

ZIC5 promotes aggressiveness and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: Cervical cancer is one of the major malignancies causing morbidity and mortality in women in developing countries. ZIC5 has been found to be associated with a variety of cancers, yet the expression and molecular function of ZIC5 in cervical squamous cell carcinoma (CESC) is unknown. METHODS: We examined the expression of ZIC5 in tumors and normal tissues of CESC patients using immunohistochemistry, immunoblotting and fluorescent quantitative PCR, and used statistical methods to explore its relationship with clinical manifestations. Next, we constructed ZIC5 knockdown and overexpression CESC cell lines to observe the effect of ZIC5 on the proliferation and metastasis of CESC cells. Finally, we applied a nude mouse xenograft tumor model to observe the effect of ZIC5 on tumorigenesis in vivo. RESULTS: Our results showed that the expression of ZIC5 was higher in cancer tissues than in normal tissues. Prognostic analysis showed that ZIC5 expression level was an independent prognostic factor in CESC patients, and the results of Transwell, CCK-8 and wound healing assays confirmed that overexpression of ZIC5 could promote the proliferation and migration of CESC cells. A nude mouse xenograft tumor model showed that knockdown of ZIC5 inhibited tumor growth in vivo. Database, immunoblotting assay and in vitro sphere-forming assay confirmed that ZIC5 could promote the stemness of CESC cells. CONCLUSION: ZIC5 is a factor that indicates a poor prognosis of CESC patients and promotes stemness in CESC cells. ZIC5 may be a potential biomarker and therapeutic target for CESC patients.