Cervical cancer is a malignant gynecological tumor, and cancer cell metastasis remains poorly controlled despite surgery, radiotherapy, and chemotherapy. Traditional Chinese medicine, with advantages of multi-target effects and low toxicity, has emerged as an important therapeutic approach. In this study, we screened Amygdalin-related targets and cervical cancer differentially expressed genes using databases (SwissTargetPrediction, TCGA). Key modules were identified via WGCNA, and core targets (CA9 and HK2) were determined through PPI network analysis and the MCODE algorithm. Single-cell RNA sequencing further localized Amygdalin-affected cell populations. Molecular docking and molecular dynamics simulations verified the binding affinity of Amygdalin to CA9 and HK2, which were further confirmed by enzymatic activity assays. These key targets were upregulated in cervical cancer tissues, significantly correlated with patient survival, and exhibited good diagnostic value (ROC curve AUC > 0.9). Cell experiments have shown that Amygdalin inhibits the proliferation of cervical cancer HeLa and SiHa cells in a dose- and time-dependent manner, and induces cell apoptosis. Amygdalin-treated HeLa cells were arrested at the G1 phase, while Amygdalin-treated SiHa cells were arrested at the G2 phase. Finally, RNA-seq transcriptomics analysis elucidated the pathway regulation mechanisms. Collectively, this study systematically confirms that Amygdalin exerts significant anti-cervical cancer effects by targeting CA9 and HK2 to regulate multiple pathways, providing an experimental and theoretical basis for its development as a candidate drug for cervical cancer treatment.

Understanding therapy resistance requires deconvolving heterogeneous cell populations and tracking clonal trajectories. While CRISPR-based cellular barcoding is powerful for lineage tracing, many platforms suffer from low efficiency and limited compatibility with single-cell transcriptomics. We developed Oligo-CALL (Oligonucleotide-inducible CRISPR transcriptional activator-Assisted Lineage Labeling), an advanced barcoding system enabling precise lineage tracing, live clone isolation, and seamless integration with single-cell RNA sequencing. Applied to lung cancer cells treated with a KRASG12C inhibitor, Oligo-CALL identified clones consistently enriched posttreatment, supporting a model of predestined resistance. Oligo-CALL achieved >95% efficiency in linking lineage identity to transcriptomes, uncovering diverse clone-specific pathways with underlying resistance. Paired analysis of barcode-matched clones from naïve and resistant populations revealed transient and fixed resistance phenotypes. Notably, DNA repair pathways are recurrently altered in resistant clones, and inhibition of poly(adenosine 5'-diphosphate-ribose) polymerase synergizes with KRAS G12C inhibition to overcome resistance. Together, Oligo-CALL provides a versatile platform for dissecting lineage evolution and molecular dynamics of targeted therapy resistance.

The LRIG gene family consists of LRIG1-3. While LRIG2 has been described as a tumor promoter, LRIG1 and LRIG3 have been identified as tumor suppressors in previous literature. Because of these contrasting roles, the expression of LRIG1-3 was examined across different grades of glioma, between primary and secondary glioblastoma and with focus on chemotherapy treatment. Human tumor tissue samples were extracted during neurosurgery and grouped among the WHO classification valid at the time of surgery. Quantitative western blot analysis, qPCR and immunofluorescence staining were performed. LRIG1 was less expressed in glioma compared to peritumoral tissue with additional decrease with ascending tumors grade. Further, secondary glioblastoma expressed more LRIG1 protein than primary. On mRNA level, the same was seen for LRIG2, were low grade glioma expressed significantly more LRIG2 than high grade glioma. And on protein level, secondary glioblastoma showed higher expression than primary. LRIG3 mRNA expression, in contrast, was significantly higher in grade II gliomas compared to surrounding control tissue, whereas chemotherapy did not significantly affect expression levels in glioblastoma. Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.

Colorectal Cancer (CRC) is the third most prevalent malignancy, leading to significant morbidity and mortality globally. Epidemiological studies suggest that chronological age and diet are among the major contributing factors correlated with the incidence of CRC. Our study aimed to provide insights into the association between age, diet, and gut microbiome in CRC using molecular techniques including RNA sequencing, cytokine analysis, and metagenomic analysis. We used syngeneic MC38 mice model divided into two age groups (old and young) and three diet groups (standard chow, calorie-restricted and high-fat). The major findings of this study are that age and diet impact intratumoral gene signaling (nuclear and mitochondrial), and hub genes we identified are associated with prognosis in CRC. Fecal microbiome analysis showed that old microbiomes have higher alpha diversity compared to young mice. Our results demonstrate that interactions between host (age) and external (diet) factors regulate tumor growth mediated by cytokines, mitochondrial derived proteins, and the gut microbiome. Collectively, our findings advance current understanding of the mechanisms by which aging, diet and gut microbiota impact CRC onset and progression though further investigation is warranted.

Glioblastoma multiforme (GBM) is a complex and aggressive central nervous system (CNS) tumor that has a poor prognosis, and restricted therapeutic options are available despite the increasing research conducted. Moreover, the cells in our body package microRNAs, ubiquitous modulators of numerous biological processes, into exosomes for cell-to-cell signaling. Indeed, exosomal miRNAs contribute to several aspects of glioma, such as development, occurrence, metastasis, and immune evasion. Additionally, exosomal miRNAs play a key role in cellular functions and glioma pathogenesis by regulating numerous pathways, including the Wnt/β-catenin, PTEN/PI3K/Akt, EGFR/MAPK, notch signaling, and NF-κB. Notably, exosomal miRNAs are recognized to have promising potential in clinical applications; in fact, exosomal miRNAs are emerging biomarkers for glioma diagnosis and prognosis and are additionally considered as putative therapeutic candidates by inhibiting tumor progression, occurrence, and metastasis. This review presents the current knowledge regarding clinical potential and application of exosomal miRNAs in glioma, as well as the miRNA-mediated regulatory network underlying glioma immunopathogenesis.

Pleomorphic adenoma (PA) is the most common benign salivary gland tumor, yet its histologic diversity can resemble malignant neoplasms, posing diagnostic challenges. Molecular characterization, including fusion gene analysis, can aid in distinguishing these cases.

Gains of chromosome 12p11.21, encoding for the cancer-specific lncRNA LISRR, correlate with poor survival across different cancers. In melanoma, LISRR is upregulated in immunotherapy-resistant patients to contribute to the generation of drug-tolerant cells by activating an immune-suppressive translational program, affecting the synthesis of PD-L1 and of the glycocalyx. Accordingly, downregulation of LISRR initiates robust immune responses and resensitizes to immunotherapy ex vivo and in vivo. The use of glycans to evade immunity exhibits shared characteristics with the testis, where defects in the glycocalyx cause infertility. Mechanistically, we showed that LISRR affects the ribosome core composition and recruits deleted in azoospermia-associated protein 1 to polysomes to prime the integrated stress response. Our study reveals the contribution of lncRNAs to the generation of cancer-specific ribosomes and identifies an RNA-based strategy to overcome resistance to immune checkpoint blockade.

Glioblastoma multiforme (GBM), the most invasive primary malignant tumor of the central nervous system, is characterized by an extremely poor prognosis and a high recurrence rate. Its significant molecular heterogeneity challenges precise diagnosis and treatment. Recently, with the rapid development of molecular pathology, the combination of histological and molecular typing has become the mainstream method for GBM diagnosis. Here, we review the impact of classic molecular markers on patient prognosis in GBM, as well as the different values of traditional and novel molecular markers in prognosis assessment. We initially discuss the correlation between molecular markers and recurrence, as well as the research progress of molecular markers in emerging technological fields. Moreover, we propose the challenges currently faced by molecular markers in glioblastoma and discuss future research directions in this field.

The divergent loop structures of nicotinic acetylcholine receptor (nAChR) α3, α5, and α7 subunits (encoded by CHRNA3, CHRNA5, and CHRNA7) are involved in kinase phosphorylation and signal transduction, potentially affecting oral squamous cell carcinoma (OSCC), the most common head and neck cancer (HNC). However, their specific roles in OSCC remain unclear.

The present study aimed to investigate the effect of microRNA (miR)-199a-3p on the biological function of non-small cell lung cancer (NSCLC) adenocarcinoma cells by targeting the fat mass and obesity‑associated protein (FTO)/myeloid zinc finger 1 (MZF1)/claudin domain‑containing 1 (CLDND1) axis. Human NSCLC cell lines, primarily A549 cells, were used for in vitro assays. Reverse transcription‑quantitative PCR and western blotting were performed to assess the expression of relevant genes and proteins. Dual‑luciferase reporter assays were used to verify the relationship between miR‑199a‑3p and FTO, as well as the transcriptional regulation of CLDND1 by MZF1. Methylated RNA immunoprecipitation was used to evaluate the N6‑methyladenosine (m6A) modification levels of MZF1, whereas photoactivatable ribonucleoside‑enhanced crosslinking and immunoprecipitation supported the binding of FTO to MZF1 mRNA. Cell proliferation, migration, invasion and apoptosis were assessed using Cell Counting Kit‑8, Transwell and flow cytometry assays. miR‑199a‑3p was downregulated in NSCLC tissues and cells. Overexpression of miR‑199a‑3p inhibited A549 cell proliferation, invasion and migration. Mechanistically, miR‑199a‑3p directly targeted and suppressed FTO, an m6A demethylase, leading to enhanced m6A modification of MZF1 mRNA and a subsequent decrease in MZF1 expression. Knockdown of MZF1 attenuated the oncogenic effects mediated by FTO, confirming that MZF1 served as a downstream effector of the miR‑199a‑3p/FTO axis. Moreover, MZF1 transcriptionally activated CLDND1, thereby facilitating the malignant phenotype of NSCLC cells. Collectively, these findings demonstrate that miR‑199a‑3p suppresses NSCLC progression by targeting FTO, promoting m6A methylation‑dependent downregulation of MZF1, and consequently decreasing CLDND1 expression. Thus, the miR‑199a‑3p/FTO/MZF1/CLDND1 axis may serve as a promising therapeutic target in NSCLC.

A highly efficient siRNA vector (PFS-CA) capable of selectively silencing genes in cancer cells was obtained by modifying common low-molecular-weight (LMW) polyethylenimine (PEI) with a bioreducible targeted multifunctional module (FS) to get PFS, followed by noncovalently incorporating chlorogenic acid (CA). FS combined folate receptor-mediated targeting for cancer cells with glutathione (GSH)-responsive siRNA release into the cytoplasm. CA, a highly biocompatible natural polyphenol served as a siRNA condensation enhancer, siRNA stabilizer, and ROS scavenger. Consequently, by the synergistic effects between PFS and CA, PFS-CA performs very well on several crucial siRNA delivery processes, including siRNA condensation, complex stability, cell uptake, endosome escape, and siRNA cytoplasmic release. The representative PFS4-3CA exhibited superior transfection efficiency in a variety of cancer cell lines, including neurogenic tumor-related PC12 cells, than commercial PEI25k and Lipo2k, and extremely high and selective gene silencing effects in cancer cells (with a gene silencing rate of 98.6% in HepG2 while only 8.4% in HK-2). Our findings demonstrated great promise for the development of a safe and effective siRNA carrier for future applications in tumor-targeted siRNA therapy.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the first two lanes of the Actin blot in Fig. 1D looked strikingly similar to the Actin panels in Fig. 2E for the MDA‑MB‑231 cell line, In addition, the Actin panel in Fig. 4A (showing a time series) looked very similar to the Actin panel in Fig. 4B (showing different treatments). Upon analyzing the data independently in the Editorial Office, it came to light that there was an overlapping pair of data panels for the immunohistochemical data shown in Fig. 6C, such that data which were intended to show the results from differently performed experiments appeared to have been derived from the same original source, and data featured in Fig. 6D had subsequently appeared in a paper published in the journal Tumor Biology that was written by different authors at different research institutes. The authors were contacted by the Editorial Office to offer an explanation for these possible anomalies in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Oncology 48: 2479‑2487, 2016; DOI: 10.3892/ijo.2016.3483].

Schisantherin A (Sch A), a compound derived from Schisandra chinensis, has anti‑inflammatory, antitumor, neuroprotective and antifibrotic properties. However, to the best of our knowledge, the role of Sch A in non‑small cell lung cancer (NSCLC) has not yet been reported. The purpose of the present study was to determine whether Sch A can prevent the development of NSCLC and to elucidate the underlying mechanisms involved. The results of the present study demonstrated that Sch A inhibited the viability of A549 and HCC827 cells. Furthermore, Sch A increased the intracellular Fe2+ level, reduced the mitochondrial membrane potential and depleted the glutathione content in lung cancer cells. These effects were reversed by the ferroptosis inhibitors ferrostatin‑1 and deferoxamine. Bioinformatics analysis and reverse transcription‑quantitative PCR results suggested that Sch A increased the mRNA levels of the transcription factor yes‑associated protein (YAP). Additionally, Sch A upregulated the expression of YAP and ferroptosis‑related proteins, including acyl‑CoA synthase long‑chain family member 4 (ACSL4) and transferrin receptor (TfR), in lung cancer cells. Silencing of YAP led to the downregulation of its downstream targets, ACSL4 and TfR, even in the presence of Sch A. In vivo, Sch A significantly inhibited subcutaneous tumor growth in nude mice. In conclusion, Sch A may activate the YAP/ACSL4/TfR signaling axis to induce ferroptosis in NSCLC cells, positioning it as a potential small‑molecule therapeutic agent for NSCLC.

To assess whether miRNA expression can be a biomarker for distinguishing between hyperplastic and adenomatous polyps and colon cancer tissues.

Ovarian cancer is one of the most malignant tumors in women. Long noncoding RNAs have been demonstrated to regulate multiple biological processes, including cell proliferation, migration, apoptosis, and drug resistance, in various cancers. Small nucleolar RNA (snoRNA) host genes (SNHGs) are a group of long noncoding RNAs. Studies have reported that SNHGs are aberrantly expressed in many kinds of cancers and are associated with poor patient prognosis. In ovarian cancer, SNHGs play critical roles in the development and progression of ovarian cancer via different pathways. However, there is a lack of systematic reports on the research progress of SNHGs in ovarian cancer. Therefore, we reviewed the studies on the roles of SNHGs in the early diagnosis, development, and treatment of ovarian cancer and explored the underlying mechanisms to provide new insights into the treatment of ovarian cancer.

Breast cancer is the leading cause of cancer-related mortality in women, with triple-negative breast cancer (TNBC) being an aggressive subtype associated with poor prognosis and limited treatment options. TNBC is known for its immunogenic characteristics, including high genetic instability and elevated tumor-infiltrating lymphocytes (TILs). Immune checkpoint inhibitors (ICIs) have shown efficacy in TNBC treatment, but the optimal treatment duration in case of prolonged response remains unclear.

Ferroptosis, a regulated form of iron-dependent cell death, has shown promise as an anti-tumor mechanism. However, its role in pancreatic cancer remains largely unexplored. This study aimed to identify a ferroptosis-related prognostic signature and key biomarkers.

Extramedullary Plasmacytoma (EMP) is a rare plasma cell neoplasm that originates outside the bone marrow. Primary Extramedullary Plasmacytoma with Diffuse Lymph Node Involvement (PLNEMP) is exceptionally rare. Here, we report a unique case of PLNEMP and significant bone destruction, characterized by a novel IGH::NFKB1 fusion gene. A 60-year-old Chinese male presented with palpable enlarged lymph nodes in the left inguinal region. After completing laboratory tests and examinations, it was suggested that there was monoclonal immunoglobulinemia and multiple bone destruction. Pathological examination of the left inguinal lymph node biopsy showed plasmacytoma with monoclonal gammopathy. Genomic profiling identified a novel IGH::NFKB1 fusion gene. The two 3' regulatory region (3'RR) enhancers of the IGH locus were fused to a region 379 bp upstream of NFKB1 exon 1, resulting in overexpression of NFKB1. The patient received four cycles of chemotherapy with Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with Bortezomib, Pomalidomide, and Dexamethasone (MVPD), achieving very good partial remission (VGPR) in hematological and partial remission (PR) in extramedullary disease. Subsequently, he underwent autologous stem cell transplantation (ASCT) followed by BCMA CAR-T cell therapy. At 8 months post-transplantation, complete remission (CR) was achieved in hematological parameters, and the extramedullary disease showed a response greater than PR. The patient has survived for 26 months so far. This case highlights the importance of recognizing the rare presentation of PEMP with diffuse lymph node involvement and significant bone destruction. The presence of the novel IGH::NFKB1 fusion gene provides insights into the potential role of the NF-κB pathway in the pathogenesis of this disease. The successful treatment with MVPD chemotherapy, ASCT, and BCMA CAR-T therapy demonstrates the potential efficacy of this combined therapeutic approach in achieving long-term remission and survival in such rare cases. Further studies are warranted to explore the therapeutic implications of targeting the NF-κB pathway in similar cases of EMP with bone destruction.

Colorectal cancer (CRC) is the third most common malignancy worldwide and the second leading cause of cancer-related deaths. Its progression is driven by genetic and epigenetic alterations, with increasing evidence emphasizing the role of the transcriptome, particularly post-transcriptional modifications. Human antigen R (HuR), an RNA-binding protein (RBP), plays a crucial role in post-transcriptional regulation of gene expression. In the context of tumor progression, HuR affects a range of cellular processes, including cell proliferation, survival, and metabolic reprogramming, via regulating target mRNA stability and translation. Additionally, HuR influences the tumor microenvironment (TME) through modulating target mRNAs involved in inflammation, immune responses, extracellular matrix remodeling and angiogenesis. Despite these insights, the precise mechanisms by which HuR regulates post-transcriptional process in CRC remain unclear. This review first provides an overview of HuR's roles and the underlying mechanisms involved in CRC progression, including its regulation of mRNA expression, control of the cell cycle, and modulation of the TME. We also discussed the potential of HuR as a therapeutic target, exploring how targeting HuR could slow down CRC progression and metastasis, ultimately leading to more effective and personalized treatment strategies.

This study aimed to validate secreted biomarkers SPON2 and MSMB with tumor-specific expression and immunogenicity for nanomaterial-based prostate cancer diagnostics.