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Abstract Background Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. Methods In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments. Results Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-β treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-β-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-β/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-β/Smad signaling pathway in NSCLC cells. Conclusion In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-β/Smad signaling pathway and represents a novel therapeutic target for NSCLC.

Abstract M2‐polarized tumor‐associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs‐derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis‐dependent manner. It is identified that MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ‐catenin protein and suppressed its ubiquitination and degradation by β‐TRCP. In addition, MALAT1 upregulated HIF‐1α expression by acting as a sponge for miR‐217‐5p. The activation of β‐catenin and HIF‐1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual‐targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome‐mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs‐derived exosomes promote gastric cancer progression via MALAT1‐mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Pre-eclampsia (PE), a major cause of perinatal morbidity and mortality, accounts for up to 14 % mortality of maternal and 18 % of fetal or infant mortalities. However, the pathogenesis process of PE remains unclear. The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the peripheral blood exosomes of early-onset PE patients versus healthy pregnant women using high-throughput sequencing, and to find candidate miRNAs as molecular markers. Methods: Peripheral blood samples were collected from five preeclamptic patients and five healthy women. Exosomal miRNAs were sequenced using the Illumina HiSeq4000 sequencing platform. The target gene prediction, biological function enrichment, and signaling pathway prediction of the miRNAs with significant differences were carried out using the Starbase database software, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Our results showed 65 significantly differentially expressed miRNAs in the exosomes of early-onset PE patients compared to control group, with 17 up-regulated and 48 down-regulated (P

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.

Abstract Background Spalt-like protein 4 (SALL4) is a stemness-related transcription factor whose abnormal re-expression contributes to cancer initiation and progression. However, the role of SALL4 in cancer angiogenesis remains unknown. Methods Analyses of clinical specimens via TCGA datasets were performed to determine the expression level and clinical significance of SALL4 in STAD (Stomach Adenocarcinoma). SALL4 knockdown, knockout, and overexpression were achieved by siRNA, CRISPR/Cas9, and plasmid transfection. The effects of conditioned medium (CM) from SALL4 knockdown or overexpression of gastric cancer cells on endothelial cell proliferation, migration, and tube formation were investigated by CCK-8 assay, transwell migration assay, and tube formation assay. The regulation of VEGF gene expression by SALL4 was studied by qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assay, and electrophoretic mobility shift assay (EMSA). Engineered exosomes from 293T cells loaded with si-SALL4-B and thalidomide were produced to test their therapeutic effect on gastric cancer progression. Results SALL4 expression was increased in STAD and positively correlated with tumor progression and poor prognosis. SALL4-B knockdown or knockout decreased while over-expression increased the promotion of human umbilical vein endothelial cells (HUVEC) cell proliferation, migration, and tube formation by gastric cancer cell-derived CM. Further investigation revealed a widespread association of SALL4 with angiogenic gene transcription through the TCGA datasets. Additionally, SALL4-B knockdown reduced, while over-expression enhanced the expression levels of VEGF-A, B, and C genes. The results of ChIP and EMSA assays indicated that SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription, which may be associated with increased histone H3-K79 and H3-K4 modifications in their promoter regions. Furthermore, si-SALL4-B and thalidomide-loaded exosomes could be efficiently uptaken by gastric cancer cells and significantly reduced SALL4-B and Vascular Endothelial Growth Factor (VEGF) expression levels in gastric cancer cells, thus inhibiting the pro-angiogenic role of their derived CM. Conclusion These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression. Co-delivery of the functional siRNA and anticancer drug via exosomes represents a useful approach to inhibiting cancer angiogenesis by targeting SALL4/VEGF pathway.

Abstract tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that are generated from cleavage of mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification of increasing number of tRFs with critical functions in distinct physiological and pathophysiological processes. tRFs can regulate cell viability, differentiation, and homeostasis through multiple mechanisms and are thus considered as critical regulators of human diseases including cancer. In addition, increasing evidence suggest the extracellular tRFs may be utilized as promising diagnostic and prognostic biomarkers for cancer liquid biopsy. In this review, we focus on the biogenesis, classification and modification of tRFs, and summarize the multifaceted functions of tRFs with an emphasis on the current research status and perspectives of tRFs in cancer.

Abstract Background Increasing studies suggest that circular RNAs (circRNAs) are critical regulators of cancer development and progression. However, the biological roles and mechanisms of circRNAs in gastric cancer (GC) remain largely unknown. Methods We identified the differentially expressed circRNAs in GC by analyzing Gene Expression Omnibus (GEO) datasets. We explored the biological roles of circRNAs in GC by in vitro functional assays and in vivo animal studies. We performed tagged RNA affinity purification (TRAP), RNA immunoprecipitation (RIP), mass spectrometry (MS), RNA sequencing, luciferase reporter assays, and rescue experiments to investigate the mechanism of circRNAs in GC. Results Downregulated expression of circular RNA EIF4G3 (circEIF4G3; hsa_circ_0007991) was found in GC and was associated with poor clinical outcomes. Overexpression of circEIF4G3 suppressed GC growth and metastasis through the inhibition of β-catenin signaling, whereas knockdown of circEIF4G3 showed the opposite effects. Mechanistic studies revealed that circEIF4G3 bound to δ-catenin protein to promote its TRIM25-mediated ubiquitin degradation and interacted with miR-4449 to upregulate SIK1 expression. Conclusion Our findings uncovered a tumor suppressor function of circEIF4G3 in GC through the regulation of δ-catenin protein stability and miR-4449/SIK1 axis. CircEIF4G3 may act as a promising prognostic biomarker and therapeutic target for GC.

Abstract Extracellular vesicles (EVs) are cell‐derived nanosized vesicles that mediate cell‐to‐cell communication via transporting bioactive molecules and thus are critically involved in various physiological and pathological conditions. EVs contribute to different aspects of cancer progression, such as cancer growth, angiogenesis, metastasis, immune evasion, and drug resistance. EVs induce the resistance of cancer cells to chemotherapy, radiotherapy, targeted therapy, antiangiogenesis therapy, and immunotherapy by transferring specific cargos that affect drug efflux and regulate signaling pathways associated with epithelial‐mesenchymal transition, autophagy, metabolism, and cancer stemness. In addition, EVs modulate the reciprocal interaction between cancer cells and noncancer cells in the tumor microenvironment (TME) to develop therapy resistance. EVs are detectable in many biofluids of cancer patients, and thus are regarded as novel biomarkers for monitoring therapy response and predicting prognosis. Moreover, EVs are suggested as promising targets and engineered as nanovehicles to deliver drugs for overcoming drug resistance in cancer therapy. In this review, the biological roles of EVs and their mechanisms of action in cancer drug resistance are summarized. The preclinical studies on using EVs in monitoring and overcoming cancer drug resistance are also discussed.

Abstract Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged as a revolutionary strategy for cancer diagnosis and prognosis prediction. Exosomes are a subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient cells and play a crucial role in mediating intercellular communication. Increasing studies suggest that exosomes have a great promise to serve as novel biomarkers in liquid biopsy, since large quantities of exosomes are enriched in body fluids and are involved in numerous physiological and pathological processes. However, the further clinical application of exosomes has been greatly restrained by the lack of high-quality separation and component analysis methods. This review aims to provide a comprehensive overview on the conventional and novel technologies for exosome isolation, characterization and content detection. Additionally, the roles of exosomes serving as potential biomarkers in liquid biopsy for the diagnosis, treatment monitoring, and prognosis prediction of cancer are summarized. Finally, the prospects and challenges of applying exosome-based liquid biopsy to precision medicine are evaluated.

As an abundant component of tumor microenvironment, cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that play important roles in tumor development, progression and therapeutic resistance. Multiple sources of cells can be recruited and educated to become CAFs, such as fibroblasts, mesenchymal stem cells and adipocytes, which may explain the phenotypic and functional heterogeneity of CAFs. It is widely believed that CAFs regulate tumor progression by remodeling extracellular matrix, promoting angiogenesis, and releasing soluble cytokines, making them a promising cancer therapy target. In this review, we discussed about the origin, subpopulation, and functional heterogeneity of CAFs, with particular attention to recent research advances and clinical therapeutic potential of CAFs in cancer.

Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.

Long non-coding RNA (lncRNA) DANCR (also known as ANCR)—differentiation antagonizing non-protein coding RNA, was first reported in 2012 to suppress differentiation of epithelial cells. Emerging evidence demonstrates that DANCR is a cancer-associated lncRNA abnormally expressed in many cancers (e.g., lung cancer, gastric cancer, breast cancer, hepatocellular carcinoma). Increasing studies suggest that the dysregulation of DANCR plays critical roles in cancer cell proliferation, apoptosis, migration, invasion, and chemoresistance in vitro and tumor growth and metastasis in vivo. Mechanistic analyses show that DANCR can serve as miRNA sponges, stabilize mRNAs, and interact with proteins. Recent research reveals that DANCR can be detected in many body fluids such as serum, plasma, and exosomes, providing a quick and convenient method for cancer monitor. Thus DANCR can be used as a promising diagnostic and prognostic biomarker and therapeutic target for various types of cancer. This review focuses on the role and mechanism of DANCR in cancer progression with an emphasis on the clinical significance of DANCR in human cancers.

Abstract Exosomes are nanosized extracellular vesicles that can be released by almost all types of cells. Initially considered as the garbage bins acting to discard unwanted products of cells, exosomes are now recognized as an important way for cellular communication by transmitting bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. The recent studies have shown that exosomes are critically involved in human health and diseases including cancer. Exosomes have been suggested to participate in the promotion of tumorigenesis, tumor growth and metastasis, tumor angiogenesis, tumor immune escape, and tumor therapy resistance. Increasing evidence indicate that exosomes play important roles in gastric cancer development and progression. In this review, we summarized the current understanding of exosomes in gastric cancer with an emphasis on the biological roles of exosomes in gastric cancer and their potential as biomarkers for gastric cancer diagnosis as well as potential targets for gastric cancer therapy.

The water sensitivity of metal-organic frameworks (MOFs) as a common and crucial issue has greatly hindered their practical applications. Here, we present a facile and general approach to improve the water resistance of a typical MOF, i.e., CuBTC [Cu3(BTC)2(H2O)3]n (BTC = benzene-1,3,5-tricarboxylate) using a post-modification reaction with aminopropyltriethoxylsilane (APTES) at room temperature. The afforded material is denoted as CuBTC@APTES. Various spectroscopic methods reveal that the organosilicon linkers have been successfully grafted onto CuBTC by electrostatic attraction between acid and base groups and without affecting the original coordination mode and basic structure. Compared with CuBTC, the water stability of CuBTC@APTES was significantly improved. The pristine CuBTC almost lost all its crystallinity, morphology and pore structure after 3-day treatment in water, while CuBTC@APTES is able to retain its main crystal structure and basic porosity after the same treatment. This finding can be explained by the successful introduction of the organosilicon molecular overlayer on the periphery of CuBTC to slow down the destruction of weak metal coordination bonds by water molecules, thus improving the water stability of CuBTC. The solution of water sensitivity provides more opportunities for the practical applications of CuBTC, such as aqueous phase catalysis and gas separation in humid environments. This simple approach can certainly be expanded to improve the water resistance of other carboxylate-containing ligand-based MOFs.

Abstract Background Long non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. However, the functional roles of lncRNAs and the mechanisms responsible for their aberrant expression in gastric cancer (GC) have not been well characterized. Methods In this study, we examined the expression of lncRNA UFC1 in GC by qRT-PCR and explored its correlation with clinicopathological parameters. In vitro cell functional assays and in vivo animal studies were performed to determine the roles of UFC1 in GC progression. Results UFC1 was elevated and predicted poorer prognosis in GC. UFC1 knockdown inhibited while UFC1 overexpression promoted GC cell proliferation, migration, and invasion. UFC1 bound to miR-498 to antagonize its tumor suppressive effect on Lin28b. Suppression of Lin28b by miR-498 could be rescued by UFC1 overexpression, whereas Lin28b overexpression partially rescued UFC1 knockdown-mediated inhibition of GC cell function. Lin28b expression was increased in GC and suggested a co-expression pattern with UFC1. Conclusions UFC1 has a promoting role in GC progression, at least in part, by acting as a miR-498 sponge and derepressing Lin28b expression, which would provide a novel biomarker for GC diagnosis and prognosis and offer a potential target for GC therapy.

BACKGROUND: Mesenchymal stem cells (MSCs) promote tumor growth by differentiating into carcinoma-associated fibroblasts (CAFs) and composing the tumor microenvironment. However, the mechanisms responsible for the transition of MSCs to CAFs are not well understood. Exosomes regulate cellular activities by mediating cell-cell communication. In this study, we aimed to investigate whether cancer cell-derived exosomes were involved in regulating the differentiation of human umbilical cord-derived MSCs (hucMSCs) to CAFs. METHODOLOGY/PRINCIPAL FINDINGS: We first showed that gastric cancer cell-derived exosomes induced the expression of CAF markers in hucMSCs. We then demonstrated that gastric cancer cell-derived exosomes stimulated the phosphorylation of Smad-2 in hucMSCs. We further confirmed that TGF-β receptor 1 kinase inhibitor attenuated Smad-2 phosphorylation and CAF marker expression in hucMSCs after exposure to gastric cancer cell-derived exosomes. CONCLUSION/SIGNIFICANCE: Our results suggest that gastric cancer cells triggered the differentiation of hucMSCs to CAFs by exosomes-mediated TGF-β transfer and TGF-β/Smad pathway activation, which may represent a novel mechanism for MSCs to CAFs transition in cancer.

Cancer vaccines stimulate the immune system within the body by introducing tumor antigens in various forms, such as tumor cells, tumor‐related proteins or peptides, and genes expressing tumor antigens, into the body. This activation of the immune response aims to prevent or treat tumors. Preventive cancer vaccines are primarily targeted at cancers caused by viral infections, and most cancer vaccines are currently designed as therapeutic vaccines for cancer treatment. In this review, the development of cancer vaccines, the mechanism of action, the types of antigens, and the progress of nanotechnology in therapeutic cancer vaccines are summarized. The development and application of cancer vaccines incorporating tumor‐specific antigens and nanomaterials are anticipated.

Abstract Radioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is involved in the deacetylation of p53 in regulating cell cycle and is associated with cancers at the molecular level. In this study, we evaluated the prognostic value in hepatocellular carcinoma (HCC) based on data from The Cancer Genome Atlas (TCGA) database. Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between DNTTIP1 expression and clinicopathological features. Cox regression and the Kaplan–Meier method were adopted to evaluate prognosis-related factors. Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to DNTTIP1. The correlations between DNTTIP1 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis (ssGSEA). DNTTIP1 was found to be upregulated with amplification in tumor tissues in multiple HCC cohorts. High DNTTIP1 expression was associated with poorer overall survival (OS) and disease-free survival (DFS). GSEA suggested that DNTTIP1 regulates the cell cycle mitotic, G1/S, and G2/M phases and Fc fragment of IgE receptor I (FCERI)–mediated NF-κB and MAPK pathway and Fc fragment of IgG receptor (FCGR) activation pathways. Notably, ssGSEA indicated that DNTTIP1 expression was positively correlated with infiltrating levels of Th2 cells, Tfh, NK CD56 bright cells, aDCs, T helper cells, Th1 cells, and macrophages. These findings suggest that DNTTIP1 is correlated with prognosis and immune infiltration in HCC, which lays a foundation for further study of the immune-regulatory role of DNTTIP1 in HCC.

Objectives: It has been reported that keratinocyte differentiation factor 1 (KDF1) was related to proliferation, differentiation, and cell cycle. However, the role of KDF1 has not been reported in ovarian cancer. The present study investigated the function and the potential mechanism of KDF1 in ovarian cancer.Methods: We evaluated the prognostic value in ovarian cancer based on data from the Cancer Genome Atlas (TCGA) database. The Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between KDF1 expression and clinicopathologic features. The Cox regression and the Kaplan–Meier method were adopted to evaluate prognosis-related factors. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) gene enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed to identify the key biological process related to KDF1. Then the expression of KDF1 in ovarian cancer tissues was validated by streptavidin–peroxidase (SP) immunohistochemistry. The proliferation and invasion ability of KDF1 were determined by EdU and Transwell assay, respectively, with KDF1 gene silencing and overexpression. The mRNA expression of KDF1 was determined by qPCR. The protein expression of KDF1 was determined using the Western blot.Methods: By performing differential expression analysis on the ovarian cancer data of the TCGA database, it was found that KDF1 is highly expressed in ovarian cancer patients and associated with poorer overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients. The highly expressed KDF1 may reduce cell adhesion according to GO, KEGG, and GSEA results. After analysis combining the relevant clinical features, we found that the high expression of KDF1 is an independent prognostic factor of ovarian cancer and associated with platinum resistance and tumor metastasis in ovarian cancer. At the same time, the BioGRID database showed that there might be protein–protein interaction between KDF1 and E-cadherin. Then we further validated that the high expression of KDF1 had a close correlation with the stage and grade of ovarian cancer in ovarian cancer tissue chips. Silencing KDF1 inhibited the proliferation and invasion ability of SKOV3 cells. By contrast, ectopic expression of KDF1 promoted the proliferation and invasion ability of A2780 cells. We also found that KDF1 can interact with E-cadherin and regulate the expression of Wnt5A and β-catenin, hence activating Wnt/β-catenin pathway via in vitro and vivo experiments.Conclusions: Based on the bioinformatics analysis, in vitro experiments, and an in vivo study, it is indicated that KDF1 played an important role in ovarian cancer progression and might be a therapeutic target for patients with ovarian cancer.

Background: Dolichyl-diphosphooligosaccharide–protein glycosyltransferase non-catalytic subunit (DDOST) is an important enzyme in the process of high-mannose oligosaccharide transferring in cells. Increasing DDOST expression is associated with impairing liver function and the increase of hepatic fibrosis degrees, hence exacerbating the liver injury. However, the relation between DDOST and hepatocellular carcinoma (HCC) has not been revealed yet.Method: In this study, we evaluated the prognostic value of DDOST in HCC based on data from The Cancer Genome Atlas (TCGA) database. The relationship between DDOST expression and clinical-pathologic features was evaluated by logistic regression, the Wilcoxon signed-rank test, and Kruskal–Wallis test. Prognosis-related factors of HCC including DDOST were evaluated by univariate and multivariate Cox regression and the Kaplan–Meier method. DDOST-related key pathways were identified by gene set enrichment analysis (GSEA). The correlations between DDOST and cancer immune infiltrates were investigated by the single-sample gene set enrichment analysis (ssGSEA) of TCGA data.Results: High DDOST expression was associated with poorer overall survival and disease-specific survival of HCC patients. GSEA suggested that DDOST is closely correlated with cell cycle and immune response via the PPAR signaling pathway. ssGSEA indicated that DDOST expression was positively correlated with the infiltrating levels of Th2 cells and negatively correlated with the infiltration levels of cytotoxic cells.Conclusion: All those findings indicated that DDOST was correlated with prognosis and immune infiltration in HCC.