Abstract Objectives To investigaed the role of endoplasmic reticulum stress (ERS)-related long non-coding RNAs (lncRNAs) in stomach adenocarcinoma (STAD) using TCGA data. Methods This study integrated clinical, transcriptomic, and tumor data from the Cancer Genome Atlas (TCGA). The expression of ERS genes was evaluated, alongside their association with identified lncRNAs. Gene set enrichment analysis and immune cell infiltration analysis were performed to elucidate the biological pathways influenced by these lncRNAs. Results The study identified five lncRNAs – AC012055.1, LINC01235, LINC00571, LINC02073, and CFAP61-AS1 – strongly correlated with ERS pathways and cancer prognosis. A prognostic model based on these lncRNAs was developed and validated across low- and high-risk groups. Potential biological pathways associated with these lncRNAs were uncovered through immune cell infiltration and GSEA. Additionally, screening identified drugs potentially effective against STAD, highlighting co-expressed genes as probable therapeutic targets. Conclusions This research offers detailed insights into the molecular mechanisms of STAD, enhancing understanding of potential therapeutic targets and showing promise for clinical applications.

Abstract Solute Carrier Family 25 (SLC25) is the largest family of mitochondrial membrane proteins in the human body, consisting of 53 members. Mitochondrial phosphate carriers (MPiC), cellular iron metabolism, voltage-dependent anion channels (VDAC), and oxidative phosphorylation in the SLC25 family play dominant roles in material transport, energy metabolism, etc. SLC25 family-related proteins are involved in the regulation of the progression of a variety of cancers, including colon, gastric, and lung cancers. In addition, the SLC25 family has been implicated in endoplasmic reticulum stress (ERS) and immunity. Since SLC25 family proteins are involved in cancer progression and are associated with endoplasmic reticulum stress and immunity, exploring inhibitors of SLC25 family-related proteins is essential. However, the exact mechanism of SLC25 family-related proteins involved in cancer, as well as potential targets and SLC25 inhibitors have not been reported in the literature. This article focuses on summarizing the relevance of the SLC25 family to cancer, ERS, and immunity. This review also provides a comprehensive overview of SLC25 family-related inhibitors.

Abstract Objectives Brain metastasis is the most lethal metastatic site for patients with breast cancer, and the incidence of brain metastasis is increasing every year. Microglia act a pivotal part in promoting the proliferation and metastasis of breast cancer cells in the brain. Therefore, understanding the biological process of brain metastasis in breast cancer is important to improve therapeutic outcomes and prolong the survival of patients. Materials and Methods The role of microglia on the prognosis of patients with breast cancer with brain metastasis was verified by immunohistochemistry and the Kaplan–Meier curve. Cell experiments in vitro were used to analyze the effect of microglia on cell proliferation, migration and invasion. Knockdown of cell migration-inducing hyaluronan-binding protein (CEMIP) expression and co-culture experiments were carried out to study the mechanism of microglia on the progression of brain metastasis of breast cancer. Results We found that microglia may shorten the survival time of patients with breast cancer by regulating the expression of CEMIP in brain metastatic tumors. Co-culture experiments in vitro indicated that microglia enhance the proliferation, migration, and invasion abilities of brain metastatic breast cancer cells; however, the knockdown of CEMIP expression suppresses this effect. In addition, we also found that CEMIP expression, increased by microglia, activates the JAK2/STAT3 pathway in brain metastatic breast cancer cells, which induces the secretion of CCL2, IL-6, TGF-β, and VEGF. CCL2 recruits microglia to gather around brain metastases, whereas IL-6, TGF-β, and VEGF induce high CEMIP expression, triggering a positive feedback loop between microglia and brain metastatic breast cancer cells. Conclusions Our study proposes a possible mechanism of microglia promoting brain metastasis of breast cancer, indicating that both microglia and CEMIP may be valuable therapeutic targets for patients with breast cancer with brain metastasis.

Abstract Objectives Exosomally transferred circular RNAs (circRNAs) are critical in cancer. However, the study of exosomal circRNAs in glioma resistance remains limited. Here, we further investigated the function and mechanism of exosomal circular RNA NT5E (circNT5E) in temozolomide-resistant glioma cells (TMZ-GCs). Methods Exosomes were isolated from TMZ-GCs and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. CircNT5E, microRNA-153 (miR-153), and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) levels were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in TMZ-sensitive and TMZ-resistant GCs and in treated TMZ-GCs. In addition, the colocalization of circNT5E and miR-153 was confirmed by fluorescence in situ hybridization (FISH) and dual-luciferase reporter assays. Internalization of exosomes was observed by immunofluorescence staining. TMZ resistance, proliferation, and pAKTser473 protein levels were evaluated by a Cell Counting Kit-8 (CCK-8) assay, an EdU incorporation assay, and Western blotting, respectively. In addition, tumor growth was examined using a xenograft tumor model in nude mice. Results We first proved that circNT5E was highly abundant in exosomes derived from TMZ-GCs. Then, we discovered that circNT5E could serve as a miR-153 sponge. Finally, knockdown of circNT5E reduced TMZ resistance and cell proliferation and downregulated AKTser473 phosphorylation by targeting miR-153 in TMZ-GCs. Moreover, our data revealed that exosomes derived from TMZ-GCs also had obvious effects on inducing the TMZ resistance and proliferation of GCs. Moreover, we revealed that the packaging of circNT5E into exosomes can be driven by hnRNP A1. Conclusions Collectively, our findings proved that exosomal circNT5E transferred in a manner mediated by hnRNPA1 could accelerate TMZ resistance by targeting miR-153 in GCs, indicating that exosomal circNT5E is a therapeutic target for TMZ-resistant glioma.

Abstract Background Ovarian cancer is a prominent cause of mortality among women worldwide. A kinase anchor protein 12 (AKAP12) has been investigated, but its contribution to ovarian cancer is unclear. Objectives This study comprehensively investigates the role of AKAP12 in ovarian cancer proliferation by elucidating its underlying mechanisms and functions. Methods We compared the expression levels of AKAP12 in ovarian cancer and adjacent tissues. We subsequently established A2780 and HO8910 cell lines that have undergone AKAP12 overexpression or knockdown to verify the function of AKAP12 in ovarian cancer. To determine the effect of AKAP12 on tumorigenicity, migration, and invasion, we performed CCK-8, colony-formation, xenograft models, transwell, and wound healing assays. Furthermore, we used pathway enrichment analysis to identify Hippo signaling related to AKAP12 overexpression. Then we characterized the relevance of Hippo signaling in AKAP12-regulated tumor suppressive effects in ovarian cancer through western blot. Results Our study revealed a significant decrease in AKAP12 expression in ovarian cancer samples. Moreover, functional assays demonstrated the tumor suppressive effects of AKAP12 overexpression, inhibiting cancer cell proliferation, migration, and invasion. Consistent with these findings, mice inoculated with AKAP12-overexpressing cells exhibited slower tumor growth in our mouse xenograft model. We also observed a positive relationship between AKAP12 overexpression and Hippo pathway-related proteins. Conclusions AKAP12 plays a crucial role in the suppression of ovarian cancer through activation of the Hippo signaling pathway. Furthermore, it could be a potential target for developing new therapeutic strategies for ovarian cancer treatment.

Abstract Objectives Exploring the pathogenesis of resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Case presentation This case report describes a rare fusion of FBXO25 and SEPT14 genes in a 58-year-old male patient with chronic myeloid leukemia. The patient had been treated with tyrosine kinase inhibitors for one year. After 6 months of imatinib treatment, the patient's symptoms improved significantly and the complete blood count returned to normal, but the optimal ratio of BCR::ABL transcripts to ABL transcripts is greater than 10 % indicating treatment failure. Then we switched to a second generation TKIs to continue treatment, During the Flumatinib treatment period, the patient developed severe bone marrow suppression and exhibited additional cytogenetic abnormalities involving chromosome aberration: 47, XY,+8[5]/47, idem, inv(Y)(p11.2q11.23)[15]. By adjusting the drug dose and elevating blood cells, the patient’s BCR::ABL P210/ABL was 2.56 % after six months of Flumatinib treatment. The patient’s BCR::ABL P210/ABL consistently remained above 1 % throughout the treatment, and additional cytogenetic abnormalities were present. Next-generation sequencing revealed the recombination of exon 4 of the FBXO25 and exon 10 of the SEPT14, and this mutation has not been previously reported. Conclusions Our findings suggest that the FBXO25-SEPT14 fusion may be associated with tyrosine kinase inhibitors resistance in chronic myeloid leukemia.

Abstract Obejectives Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, comparising various subtypes including classical PTC (accounting for approximately 55–65 % of cases) and several variants. The identified variants include papillary microcarcinoma, encapsulated variant, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, cribriform-morular variant, and Warthin-like variant (WLV-PTC). WLV-PTC is a rare malignant neoplasm. Case presentation The present study introduced two cases of WLV-PTC from Affiliated Hospital of Chengde Medical College in retrospect. The macroscopic characteristics, histological feature, immunophenotyping, gene mutations, local invasion, and distant metastasis of the tumors were observed, and the relevant literature on WLV-PTC was reviewed. The tumor cells exhibited nuclear the characteristics similar to those of classic papillary thyroid carcinoma. Immunohistochemical analysis showed strong positivity for thyroid transcription factor 1, cytokeratin 19, Galectin-3, and CK, weak positivity for thyroglobulin, and the Ki-67 proliferation index ranging from 5 to 10 %. Gene mutation analysis revealed that Case 1 had a BRAF V600E mutation, whereas Case 2 had a wild-type mutation. WLV-PTC has histological features similar to those of Warthin tumor originating from salivary gland. Conclusions The prognosis of WLV-PTC is similar to that of conventional PTC of comparable size and stage.

Abstract Objectives Previous studies have shown that tripartite motif-containing 28 (TRIM28) might be a latent target for cancer therapy. However, the detailed roles and mechanisms of TRIM28 in hepatocellular carcinoma (HCC) remain ambiguous. Methods We systematically analyzed TRIM28 mRNA expression and protein levels in HCC tissues based on large-scale data and publicly available immunohistochemistry images. We estimated the prognostic capacity of TRIM28 in HCC. Additionally, we performed gene enrichment, immune infiltration, and drug sensitivity analyses to further explore the roles of TRIM28 in HCC. To determine the effect of TRIM28 expression on HCC cell proliferation and migration, successful transfection of siRNAs was conducted in MHCC97-L and Huh7 cells, followed by cell functional assays. Results We verified the overexpression of TRIM28 in HCC at the mRNA and protein levels. The summary receiver operating characteristics curve with the area under curve of 0.84 (95 % CI: 0.81–0.87) indicated the high accuracy of increasing TRIM28 expression for discriminating HCC from non-HCC tissues. According to The Cancer Genome Atlas datasets, TRIM28 mRNA expression was significantly related to age, grade, stage, and pathologic T (p<0.05). Increased TRIM28 expression levels were significant correlated to poor survival in HCC patients. An enrichment analysis suggested that TRIM28-reated genes primarily participated in the spliceosome signaling pathway, with hub genes including SNRPA1, SNRPF, SNRPD1, SF3B2, SNRPB, SNRPE, and EFTUD2. TRIM28 expression was correlated with the infiltration of five immune cells. Higher TRIM28 expression was linked to better sensitivity of tumor cells to pluripotin. Molecular docking showed that pluripotin could bind to TRIM28. Further, knockdown of TRIM28 inhibited the proliferation and migration of HCC cells. Conclusions TRIM28 is highly expressed in HCC and contribute to the proliferation and migration of HCC cells, leading to unfavorable outcomes. These findings indicate TRIM28 promise as a novel prognostic indicator.

Abstract Cell pyroptosis, an inflammatory and programmed cell necrosis, is also an important cause of multiple organ damage and immunosuppression. Pyroptosis, a new kind of programmed cell death, leads to cleavage of the pyroptotic protein Gasdermin family and ultimately to membrane pore formation, cell shrinkage, plasma membrane cleavage, chromatin disruption and release of pro-inflammatory components. Various studies found that pyroptosis had a key role in cancer and inflammatory diseases. Gasdermin family is key protein in pyrotopsis. Non-coding RNAs have a potential role in cell pyrotosis which regulate immunity and cell death. This article reviews cell pyroptosis, GSDM family and the regulatory role of non-coding RNAs.

Abstract Objectives Colorectal cancers represent the predominant malignancies affecting the gastrointestinal tract. In contrast, appendiceal tumors occur less frequently. Among them, appendiceal neuroendocrine tumors (ANETs) account for approximately 50 % of cases and are often detected incidentally during unrelated procedures. Case presentation We present an extremely rare case of an incidental neuroendocrine tumor of the appendix discovered during surgery for rectal adenocarcinoma and provide a review of the relevant literature. A 70-year-old patient with radiologically and endoscopically diagnosed rectal cancer underwent a low anterior resection with total mesorectal excision and a temporary diverting ileostomy following preoperative chemotherapy and radiation therapy. Intraoperatively, a small appendiceal mass was discovered and excised. Histopathological examination confirmed a well-differentiated NET of the appendix measuring 0.4 cm in diameter. Conclusions This case report emphasizes the importance of thorough intraoperative examination during colorectal surgeries and highlights the need for increased awareness of appendiceal NETs among surgeons.