Kidney Cancer and Potential Use of Urinary Extracellular Vesicles

Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50–200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs’ cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs’ cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis

The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals

The diagnostic value of circulating tumor DNA in hepatitis B virus induced hepatocellular carcinoma: a systematic review and meta-analysis

Background/Aim New biomarkers are urgently needed to aid in the diagnosis of early stage hepatocellular carcinoma (HCC). We performed a meta-analysis on the diagnostic utility of circulating tumor DNA (ctDNA) levels in patients with hepatitis B virus-induced HCC. Methods We retrieved relevant articles from PubMed, Embase, and the Cochrane Library up to February 8, 2022. Two subgroups were defined; one subset of studies analyzed the ctDNA methylation status, and the other subset combined tumor markers and ctDNA assays. Pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) were analyzed. Results Nine articles including 2,161 participants were included. The overall SEN and SPE were 0.705 (95% confidence interval [CI], 0.629-0.771) and 0.833 (95% CI, 0.769-0.882), respectively. The DOR, PLR, and NLR were 11.759 (95% CI, 7.982-17.322), 4.285 (95% CI, 3.098-5.925), and 0.336 (0.301-0.366), respectively. The ctDNA assay subset exhibited an AUC of 0.835. The AUC of the combined tumor marker and ctDNA assay was 0.848, with an SEN of 0.761 (95% CI, 0.659-0.839) and an SPE of 0.828 (95% CI, 0.692-0.911). Conclusions Circulating tumor DNA has promising diagnostic potential for HCC. It can serve as an auxiliary tool for HCC screening and detection, especially when combined with tumor markers

Discovery of Novel Human Breast Cancer MicroRNAs from Deep Sequencing Data by Analysis of Pri-MicroRNA Secondary Structures

MicroRNAs (miRNAs) are key regulators of gene expression and contribute to a variety of biological processes. Abnormal miRNA expression has been reported in various diseases including pathophysiology of breast cancer, where they regulate protumorigenic processes including vascular invasiveness, estrogen receptor status, chemotherapy resistance, invasion and metastasis. The miRBase sequence database, a public repository for newly discovered miRNAs, has grown rapidly with approximately >10,000 entries to date. Despite this rapid growth, many miRNAs have not yet been validated, and several others are yet to be identified. A lack of a full complement of miRNAs has imposed limitations on recognizing their important roles in cancer, including breast cancer. Using deep sequencing technology, we have identified 189 candidate novel microRNAs in human breast cancer cell lines with diverse tumorigenic potential. We further show that analysis of 500-nucleotide pri-microRNA secondary structure constitutes a reliable method to predict bona fide miRNAs as judged by experimental validation. Candidate novel breast cancer miRNAs with stem lengths of greater than 30 bp resulted in the generation of precursor and mature sequences in vivo. On the other hand, candidates with stem length less than 30 bp were less efficient in producing mature miRNA. This approach may be used to predict which candidate novel miRNA would qualify as bona fide miRNAs from deep sequencing data with approximately 90% accuracy

Cross-linkable and Degradable Layer-by-Layer Assembly under Cytocompatible Conditions for Cell-Encapsulation

Layer-by-layer (LbL) assembly has recently emerged as a highly versatile and promising method for biochemical and biomedical applications. Accordingly, it is urgently necessary to develop a cytocompatible LbL assembly technique that is stable and offers on-demand degradation and functionalization. In this study, we developed a simple and biocompatible LbL technique that cross-links the layers through covalent bonds under physiological conditions without requirement of any post-treatments or additives. By utilizing the dynamic nature of the disulfide bond, stable LbL films can be spontaneously formed during the process, further functionalized using thiol-maleimide chemistry, and degraded in response to glutathione. In addition, we demonstrated that the method is applicable to plate surfaces, spherical nanoparticles, and even living cells

The complete mitogenome of the Chionoecetes opilio (Crustacea: Decapoda: Oregoniidae) and its unique characteristics

The complete mitochondrial genome of Chionoecetes opilio is a 16,067 bp long, circular molecule which contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA genes (rRNAs). Its gene contents and organization are generally similar to other majoid mitogenomes. However, the mitogenome shows unique characteristics; long terminal amino acids, loss or addition of 3 PCGs, a 1216 bp long putative D-loop region, and peculiar secondary structures of 5 tRNAs. The concatenated amino acid sequences of 13 PCGs were used to analyze the phylogenetic tree, which well supported the monophyly of brachyuran clades of Majoidea, Heterotremata, Thoracotremata, and Eubrachyura

Dropout alignment allows homology recognition and evolutionary analysis of rDNA intergenic spacers

Subrepeats within the ribosomal gene (rDNA) intergenic spacer (IGS) play an important role in enhancing RNA polymerase I transcription. Despite this functional role and presumed selective constraint, there is surprisingly little sequence similarity among IGS subrepeats of different species. This sequence dissimilarity corresponds with the fast insertion-deletion (indel) rates observed in short mononucleotide microsatellites (here referred to as poly[N] runs, where N is any nucleotide), which are relatively abundant in rDNA IGS subrepeats. Some species have different types of IGS subrepeats that share species-specific poly(N) run patterns. This finding indicates that many IGS subrepeats within species share a common evolutionary history. Furthermore, by aligning sequences after modifying them by the dropout method, i.e., by disregarding poly(N) runs during the sequence aligning step, we sought to uncover evolutionarily shared similarities that fail to be recognized by current alignment programs. To ensure that the improved similarities in the computed alignments are not a chance artifact, we calibrated and corrected the IGS subrepeat sequences for the influence of repeat length and estimated the statistical significance of the alignments (in terms of a stringent p-value) obtained by the dropout method by comparing them to null models constructed using random sequence sets from the same genomes. We found that most diverse kinds of rDNA IGS subrepeats in one species must have been derived from a common ancestral subrepeat, and that it is possible to infer the evolutionary relationships among the IGS subrepeats of different species by comparative genomics methods based on dropout alignments.close3