Long non-coding RNAs (lncRNAs), which are important functional regulators in cancer, have received increased attention in recent years. In this study, next-generation sequencing technology was used to identify aberrantly expressed lncRNAs in follicular thyroid carcinoma (FTC). The long non-coding RNA–HLA complex P5 (HCP5) was found to be overexpressed in FTC. The results of the qPCR analysis were consistent with the sequencing results. In addition, functional experiments showed that overexpression of HCP5 can promote the proliferation, migration, invasiveness and angiogenic ability of FTC cells. Furthermore, according to the sequencing results, HCP5 and alpha-2, 6-sialyltransferase 2 (ST6GAL2) were co-expressed in FTC. We hypothesised that ST6GAL2 may be regulated by HCP5, which would in turn mediate the activity of FTC cells. Through qPCR, immunostaining analyses and functional experiments, we determined that the expression of HCP5 was elevated and was correlated with the levels of ST6GAL2 in FTC tissues and cells. Mechanistic experiments showed that HCP5 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-22-3p, miR-186-5p and miR-216a-5p, which activates ST6GAL2. In summary, our study revealed that HCP5 is a tumour regulator in the development of FTC and that it may contribute to improvement of FTC diagnosis and therapy.

The fucosyltransferase (FUT) family produces glycans, a fundamental event in several cancers, including colorectal cancer (CRC). miR-125a-3p is a non-coding RNA that can reduce cell proliferation and migration in cancer. In this study, we explored the levels of miR-125a-3p and FUT expression in human CRC tissues and two human CRC cell lines by qPCR. The results showed that miR-125a-3p, FUT5 and FUT6 are differentially expressed in normal and tumour tissues. On the basis of our previous research, FUT can be regulated by miRNA, which influences the proliferation and invasion of breast and hepatocellular cancer cells. We hypothesised that FUT5 and FUT6 may be regulated by miR-125a-3p. Luciferase reporter analyses were applied to identify potential target genes of miR-125a-3p. A functional study showed that miR-125a-3p overexpression can inhibit the proliferation, migration, invasion and angiogenesis of CRC cells via down-regulating FUT5 and FUT6. In addition, regulating miR-125a-3p, FUT5 or FUT6 expression markedly modulated the activity of the PI3K/Akt signalling pathway, and this effect of FUT5 or FUT6 could be reversed by transfection with miR-125a-3p-mimics. Taken together, our data suggest that both FUT5 and FUT6 can promote the development of CRC via the PI3K/Akt signalling pathway, which is regulated by miR-125a-3p. miR-125a-3p may serve as a predictive biomarker and a potential therapeutic target in CRC treatment.

Background: Metastasis is the main cause of mortality in cervical cancer (CC). Circular RNAs (circRNAs) have been demonstrated to play a crucial role in carcinoma biology. However, the expression and function of circRNAs in cervical cancer metastasis are still unclear.Methods: In the present study, we identified a circRNA with an N6-methyladenosine (m6A) modification, circCCDC134, whose expression was increased in CC tissues by circRNA-Seq and qPCR. CircCCDC134 upregulation in CC was fine-tuned by ALKBH5-mediated m6A modification, which enhanced its stability in a YTHDF2-dependent manner. The functional experiments illustrated that circCCDC134 enhanced tumour proliferation and metastasis in vitro and in vivo. For the comprehensive identification of RNA-binding proteins, circRNA pull-down and mass spectrometry (ChIRP-MS), chromatin immunoprecipitation-seq (Chip-seq), RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were used to perform mechanistic investigations.Results: The results revealed that circCCDC134 recruited p65 in the nucleus and acted as a miR-503-5p sponge to regulate the expression of MYB in the cytoplasm, ultimately stimulating HIF1A transcription and facilitating CC growth and metastasis. Conclusion: These findings indicate that circCCDC134 is an important therapeutic target and provide new regulatory model insights for exploring the carcinogenic mechanism of circCCDC134 in CC.

Angiogenesis has been recognized to play an essential role in remodeling new bone (osteogenesis). Small extracellular vesicles (sEVs), the endogenously secreted nanovesicles by cells, exhibit great potential in the regeneration of bone defects and the realization of cell-free therapy. Chitosan, a natural polysaccharide, can form a thermosensitive injectable hydrogel through the addition of β-glycerophosphate. Herein, we developed injectable thermosensitive hydrogel-encapsulated sEVs derived from bone mesenchymal stem cells, which significantly prolonged delivery and release and synergistically enhanced bone regeneration. sEVs were isolated and characterized, and the physicochemical properties, release kinetics, and biocompatibility of the hydrogels were analyzed. In vitro experiments were performed to investigate osteogenic differentiation, cell proliferation and migration, and tube formation. Thereafter, sEVs were added to the chitosan/β-glycerophosphate hydrogel (sEV@CS/β-GP composite) to repair calvarial defects in rats. The results showed that sEV-loaded hydrogels were biocompatible, exhibiting excellent thermosensitive properties and enhancing bone regeneration. Furthermore, mechanistic studies revealed that exosomal miR-21 targeted SPRY2, thereby promoting angiogenesis. Our study provides new insights on the repair of bone defects with multifunctional controlled-sEV-release hydrogels, which shows great potential in the repair of tissues in the future.

Hepatocellular carcinoma (HCC) samples were clustered into three energy metabolism-related molecular subtypes (C1, C2, and C3) with different prognosis using the gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). HCC energy metabolism-related molecular subtype analysis was conducted based on the 594 energy metabolism genes. Differential expression analysis yielded 576 differentially expressed genes (DEGs) among the three subtypes, which were closely related to HCC progression. Six genes were finally selected from the 576 DEGs through LASSO-Cox regression and used in constructing a six-gene signature-associated prognostic risk model, which was validated using the TCGA internal and three GEO external validation cohorts. The risk model showed that high ANLN, ENTPD2, TRIP13, PLAC8, and G6PD expression levels were associated with bad prognosis, and high expression of ADH1C was associated with a good prognosis. The validation results showed that our risk model had a high distinguishing ability of prognosis in HCC patients. The four enriched pathways of the risk model were obtained by gene set enrichment analysis (GSEA) and found to be associated with the tumorigenesis and development of HCC, including the cell cycle, Wnt signaling pathway, drug metabolism cytochrome P450, and primary bile acid biosynthesis. The risk score calculated from the established risk model in 204 samples and other clinical characteristics were used in building a nomogram with a good prognostic prediction ability (C-index = 0.746, 95% CI = 0.714–0.777). The area under the curves (AUCs) of the nomogram model in 1-, 2-, and 3-years were 0.82, 0.77, and 0.79, respectively. Then, qRT-PCR and immunohistochemistry were used to validate the mRNA expression levels of the six genes, and significant differences in mRNA and gene expression were observed among the tumor and adjacent tissues. Overall, our study divided HCC patients into three energy metabolism-related molecular subtypes with different prognosis. Then, a risk model with a good performance in prognostic prediction was built using the TCGA dataset. This model can be used as an independent prognostic evaluation index for HCC patients.

Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). The OC-specific differentially methylated regions (DMRs) were identified by sequencing ovarian tissue samples from OC (n = 61), benign ovarian disease (BOD, n = 49) and healthy controls (HC, n = 37). Based on 1,272 DMRs, a cfDNA OC detection model (OC-D model) was trained and validated in plasma samples from patients of OC (n = 104), BOD (n = 56) and HC (n = 56) and a prognostic testing model (OC-P model) was developed in plasma samples in patients with high-grade serous OC (HG-SOC) in the training cohort and then tested the rationality of this model with International Cancer Genome Consortium (ICGC) tissue methylation data. Mechanisms were investigated in the TCGA-OC cohort. In the validation cohort, the cfDNA OC-D model consisting of 18 DMRs achieved a sensitivity of 94.7% (95% CI: 85.4%‒98.9%) at a specificity of 88.7% (95% CI: 78.7%‒94.9%), which outperformed CA 125 (AUC: 0.967 vs 0.905, P = 0.03). Then the cfDNA OC-P model consisting of 15 DMRs was constructed and associated with a better prognosis of HG-SOC in multivariable Cox regression analysis (HR: 0.29, 95% CI, 0.11‒0.78, P = 0.01) in the training cohort, which was also observed in the ICGC cohort using tissue methylation (HR: 0.56, 95% CI, 0.32‒0.98, P = 0.04). Investigation into mechanisms revealed that the low-risk group had higher homologous recombination deficiency and immune cell infiltration (P < 0.05). Our study demonstrated the potential utility of cfDNA methylation in the detection and prognostic testing in OC. Future studies with a larger population are warranted. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.