eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Identification of tumor stemness and immunity related prognostic factors and sensitive drugs in head and neck squamous cell carcinoma.

The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.

Current understanding of functional peptides encoded by lncRNA in cancer.

Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

Fingerprint profiling for quality evaluation and the related biological activity analysis of polysaccharides from Liuweizhiji Gegen-Sangshen beverage.

Introduction: Liuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP. Methods: LGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated. Results: The results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity. Discussion: The results of present study would be of help to gain the understanding of structure-activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

Potential applications of dual haptoglobin expression in the reclassification and treatment of hepatocellular carcinoma.

HCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene within a subgroup of HCC malignant cells. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.

Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.

HPV-associated cervicovaginal microbiome and host metabolome characteristics.

BACKGROUND: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. RESULTS: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. CONCLUSION: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Emerging role of RNA modification and long noncoding RNA interaction in cancer.

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

Chemical profiling and quality evaluation of Liuweizhiji Gegen-Sangshen oral liquid by UPLC-Q-TOF-MS and HPLC-diode array detector fingerprinting.

INTRODUCTION: Liuweizhiji Gegen-Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated. OBJECTIVE: The aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis. METHODOLOGY: A comprehensive strategy was used by combining qualitative analysis by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and fingerprint analysis by high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS: A total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC-Q-TOF-MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples. CONCLUSION: The proposed comprehensive strategy combining HPLC-DAD fingerprinting and multi-component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines.

Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.

OBJECTIVE: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. METHODS: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. RESULTS: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. CONCLUSION: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy.

Acacetin inhibited non-small-cell lung cancer (NSCLC) cell growth via upregulating miR-34a in vitro and in vivo.

Acacetin, one of the flavonoid compounds, is a natural product found in various plants, including Silver birch, and Damiana. Previous studies showed that acacetin has anti-cancer effects on many kinds of cancer cells, however, the role of and the mechanisms of actions of acacetin on non-small cell lung cancer (NSCLC) cells is still not fully understood. Herein, we found that, in vitro, acacetin inhibited the proliferation, invasion, and migration of NSCLC cells, A549 and H460, in a dose-dependent manner. Meanwhile, flow cytometry assay results showed that acacetin induced G2/M phase cell cycle arrest, and apoptosis of NSCLC cells. In vivo, acacetin suppressed tumor formation of A549-xenografted nude mice model with no obvious toxicities. Western blotting results showed that the protein levels of cell cycle-related proteins cyclin B1, cyclin D, and anti-apoptotic protein Bcl-2 had decreased, while the apoptosis-related protein Bak had increased both in NSCLC cells and in A549-xenografted tumor tissues. For investigating the molecular mechanism behind the biological effects of acacetin on NSCLC, we found that acacetin induced the expression levels of tumor suppressor p53 both in vitro and in vivo. MicroRNA, miR-34a, the direct target of p53, has been shown anti-NSCLC proliferation effects by suppressing the expression of its target gene programmed death ligand 1 (PD-L1). We found that acacetin upregulated the expression levels of miR-34a, and downregulated the expression levels of PD-L1 of NSCLC cells in vitro and of tumors in vivo. In vitro, knockdown p53 expression by siRNAs reversed the induction effects of acacetin on miR34a expression and abolished the inhibitory activity of acacetin on NSCLC cell proliferation. Furthermore, using agomir and antagomir to overexpress and suppress the expression miR-34a in NSCLC cells was also examined. We found that miR-34a agomir showed similar effects as acacetin on A549 cells, while miR-34a antagomir could partially or completely reverse acacetin's effects on A549 cells. In vivo, intratumor injection of miR-34a antagomir could drastically suppress the anti-tumor formation effects of acacetin in A549-xenografted nude mice. Overall, our results showed that acacetin inhibits cell proliferation and induces cell apoptosis of NSCLC cells by regulating miR-34a.

Dysregulation of immunity by cigarette smoking promotes inflammation and cancer: A review.

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.

LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway.

OBJECTIVE: Emerging evidence indicates that long non-coding RNA (lncRNA) RP11-93B14.5 facilitates tumor progression in variety of malignancies. The present study proposed to study the functional effect of lncRNA RP11-93B14.5 in gastric cancer (GC) as well as the underlying mechanism. METHODS: Bioinformatics analysis was utilized to analyze lncRNA expression in GC tissues. siRNA was used for knockdown of RP11-93B14.5 in GC cells MKN45 and KATO III. The stable knockdown cell lines were constructed by CRISPR-Cas9. Cell counting kit-8 (CCK-8) assay and soft agar colony formation assay were used to analyze GC cell viability. Flow cytometry analysis was performed to analyze the cell cycle distribution of MKN45 and KATO III. RNA sequencing (RNA-seq) was employed to detect differential genes after transfection with siRP11-93B14.5. Quantitative PCR (Q-PCR) was used to examine gene expression in GC cell lines. Western-blot assay was used to measure protein levels. RNA fluorescent in situ hybridization (FISH) was conducted for lncRNA cellular location and expression. RESULTS: Based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, RP11-93B14.5 was upregulated in GC tissue, which was also verified in GC cell lines in comparison to the normal gastric epithelial HFE145 cells. Knockdown of RP11-93B14.5 decreased cell viability and the colony number of MKN45 and KATO III cells, and altered cell cycle distribution in vitro. RNA-seq analysis revealed RP11-93B14.5 may modulate genes expression of S100A2 and TIMP2 in MKN45 and KATO III cells. Mechanistically, RP11-93B14.5 may drive the progression of GC via S100A2 related-PI3K/AKT signaling pathway. CONCLUSIONS: LncRNA RP11-93B14.5 knockdown alleviated the malignant phenotypes of GC cells through regulating PI3K/AKT. Our results provide evidence for the role of lncRNAs in regulating tumor progression.

Potential role of mesenchymal stem cells in T cell aging.

Immunosenescence occurs with progressive age. T cell aging is manifested by immunodeficiency and inflammation. The main mechanisms are thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, loss of protein stability, reduction of T cell receptor (TCR) repertoire, naïve-memory T cell ratio imbalance, T cell senescence, and lack of effector plasticity. Mesenchymal stem cells (MSCs) are thought to hold great potential as anti-aging therapy. However, the role of MCSs in T cell aging remains elusive. This review makes a tentative summary of the potential role of MSCs in the protection against T cell aging. It might provide a new idea to intervene in the aging of the immune system.

Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.

Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis. Anoikis, a form of apoptosis initiated by cell detachment from the native environment, is an outside-in process commencing with the disruption of cytosolic connectors such as integrin-ECM and cadherin-cell. This disruption subsequently leads to intracellular cytoskeletal and signaling pathway alterations, ultimately activating caspases and initiating programmed cell death. Development of an anoikis-resistant phenotype is a critical initial step in tumor metastasis. Breast cancer employs a series of stromal alterations to suppress anoikis in cancer cells. Comprehensive investigation of anoikis resistance mechanisms can inform strategies for preventing and regressing metastatic breast cancer. The present review first outlines the physiological mechanisms of anoikis, elucidating the alterations in signaling pathways, cytoskeleton, and protein targets that transpire from the outside in upon adhesion loss in normal breast cells. The specific anoikis resistance mechanisms induced by pathological changes in various spatial structures during breast cancer development are also discussed. Additionally, the genetic loci of targets altered in the development of anoikis resistance in breast cancer, are summarized. Finally, the micro-RNAs and targeted drugs reported in the literature concerning anoikis are compiled, with keratocin being the most functionally comprehensive. Video Abstract.

Role of miR­181a­5p in cancer (Review).

MicroRNAs (miRNAs) are non­coding RNAs (ncRNAs) that can post­transcriptionally suppress targeted genes. Dysregulated miRNAs are associated with a variety of diseases. MiR­181a­5p is a conserved miRNA with the ability to regulate pathological processes, such as angiogenesis, inflammatory response and obesity. Numerous studies have demonstrated that miR­181a­5p exerts regulatory influence on cancer development and progression, acting as an oncomiR or tumor inhibitor in various cancer types by impacting multiple hallmarks of tumor. Generally, miR­181a­5p binds to target RNA sequences with partial complementarity, resulting in suppression of the targeted genes of miR­181a­5p. However, the precise role of miR­181a­5p in cancer remains incompletely understood. The present review aims to provide a comprehensive summary of recent research on miR­181a­5p, focusing on its involvement in different types of cancer and its potential as a diagnostic and prognostic biomarker, as well as its function in chemoresistance.

Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway.

METTL7A is a protein-coding gene expected to be associated with methylation, and its expression disorder is associated with a range of diseases. However, few research have been carried out to explore the relationship between METTL7A and tumor malignant phenotype as well as the involvement potential mechanism. We conducted our research via a combination of silico analysis and molecular biology techniques to investigate the biological function of METTL7A in the progression of cancer. Gene expression and clinical information were extracted from the TCGA database to explore expression variation and prognostic value of METTL7A. In vitro, CCK8, transwell, wound healing and colony formation assays were conducted to explore the biological functions of METT7A in cancer cell. GSEA was performed to explore the signaling pathway involved in METTL7A and validated via western blotting. In conclusion, METTL7A was downregulated in most cancer tissues and its low expression was associated with shorter overall survival. In melanoma, METTL7A downregulation was associated with poorer clinical staging, lower levels of TIL infiltration, higher IC50 levels of chemotherapeutic agents, and poorer immunotherapy outcomes. QPCR results confirm that METTL7A is down-regulated in melanoma cells. Cell function assays showed that METTL7A knockdown promoted proliferation, invasion, migration and clone formation of melanoma cells. Mechanistic studies showed that METTL7A inhibits tumorigenicity through the p53 signaling pathway. Meanwhile, METTL7A is also a potential immune regulatory factor.

Chemical profiling and investigation of molecular mechanisms underlying anti-hepatocellular carcinoma activity of extracts from Polygonum perfoliatum L.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.