MicroRNAs (miRNAs) are a group of small non-coding RNAs that are involved in regulating a range of developmental and physiological processes; their dysregulation has been associated with development of diseases including cancer. Circulating miRNAs and exosomal miRNAs have also been proposed as being useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, miRNAs are discussed as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize some of the clinical evidence for the use of miRNAs as biomarkers in diagnostics and provide some general perspectives on their use in clinical situations. The analytical challenges in using miRNAs in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics.

Development of minimally invasive biomarker assays for early detection and effective clinical management of pancreatic cancer is urgently needed to reduce high morbidity and mortality associated with this malignancy. We hypothesized that if aberrantly expressing microRNAs (miRNA) in pancreatic adenocarcinoma tissues are detected in blood plasma, then plasma profiling of these miRNAs might serve as a minimally invasive early detection biomarker assay for this malignancy. By using a modified protocol to isolate and quantify plasma miRNAs from heparin-treated blood, we show that miRNA profiling in plasma can differentiate pancreatic adenocarcinoma patients from healthy controls. We have profiled four miRNAs, miR-21, miR-210, miR-155, and miR-196a, all implicated in the development of pancreatic cancer with either proven or predicted target genes involved in critical cancerassociated cellular pathways. Of these, miR-155 has recently been identified as a candidate biomarker of early pancreatic neoplasia, whereas elevated expression of miR196a has been shown to parallel progression of disease. The results revealed a sensitivity of 64% and a specificity of 89% with the analyses of plasma levels for this panel of four miRNAs. The area under the receiver operating characteristic curve were estimated at 0.82 and 0.78 without and with leave-one-out cross-validation scheme, respectively. These observations, although a "proof of principle" finding at this time, show the feasibility of developing plasma miRNA profiling as a sensitive and specific blood-based biomarker assay for pancreatic cancer that has the potential of translation to the clinic with additional improvements in the future.

Background: The molecular identity of the intestinal vitamin C transporters is incomplete. Results: Facilitative sugar transporters, GLUT2 and GLUT8, transport dehydroascorbic acid, the oxidized form of vitamin C. Conclusion: Intestinal vitamin C absorption can occur via facilitative sugar transporters. Significance: Vitamin C bioavailability may be inhibited by dietary factors, such as glucose and phytochemicals.

MicroRNAs (miRNAs), the 17-to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in cancer, where miRNAs function either as oncogenes or as tumor-suppressor genes and are shed from cancer cells into circulation. The present review summarizes and evaluates recent advances in our understanding of the characteristics of tumor tissue miRNAs, circulating miRNAs, and the stability of miRNAs in tissues and their varying expression profiles in circulating tumor cells, and body fluids including blood plasma. These advances in knowledge have led to intense efforts towards discovery and validation of differentially expressing tumorassociated miRNAs as biomarkers and therapeutic targets of cancer. The development of tumor-specific miRNA signatures as cancer biomarkers detectable in malignant cells and body fluids should help with early detection and more effective therapeutic intervention for individual patients.

Incidence and mortality associated with hepatocellular carcinoma (HCC) is rising throughout the world. Accurate, noninvasive biomarkers for the early detection of HCC are urgently needed to reduce worldwide morbidity and mortality related to HCC. MicroRNAs (miRNAs), 17- to 25-nucleotide noncoding RNAs that are frequently dysregulated in HCC, have shown great promise as tissue-based markers for HCC diagnosis and prognosis. Moreover, they are stably expressed in serum and urine, and these circulating microRNAs (cmiRNAs) are emerging as novel noninvasive biomarkers for the early detection and prognosis of HCC. This article summarizes the latest findings on the role of circulating miRNAs as potential minimally invasive diagnostic and prognostic biomarkers for HCC.

Intraductal papillary mucinous neoplasm (IPMN) is a precursor cystic lesion to pancreatic cancer. With the goal of classifying IPMN cases by risk of progression to pancreatic cancer, we undertook an exploratory Next Generation Sequencing (NGS) based profiling study of miRNAs (miRNome) in the cyst fluids from low grade- benign and high grade- invasive pancreatic cystic lesions. Thirteen miRNAs (miR-138, miR-195, miR-204, miR- 216a, miR-217, miR-218, miR-802, miR-155, miR-214, miR-26a, miR-30b, miR-31, and miR-125) were enriched and two miRNAs (miR-451a and miR-4284) were depleted in the cyst fluids derived from invasive carcinomas. Quantitative real-time polymerase chain reaction analysis confirmed that the relative abundance of tumor suppressor miR-216a and miR-217 varied significantly in these cyst fluid samples. Ingenuity Pathway Analysis (IPA) analysis indicated that the genes targeted by the differentially enriched cyst fluid miRNAs are involved in five canonical signaling pathways, including molecular mechanisms of cancer and signaling pathways implicated in colorectal, ovarian and prostate cancers. Our findings make a compelling case for undertaking in-depth analyses of cyst fluid miRNomes for developing informative early detection biomarkers of pancreatic cancer developing from pancreatic cystic lesions.

Triple Negative Breast Cancer (TNBC) is a highly heterogeneous subtype of breast cancer that lacks the expression of oestrogen receptors, progesterone receptors and human epidermal growth factor receptor 2. Although TNBC is sensitive to chemotherapy, the overall outcomes of TNBC are worse than for other breast cancers, and TNBC is still one of the most fatal diseases for women. With the discovery of antigens specifically expressed in TNBC cells and the developing technology of monoclonal antibodies, chimeric antigen receptors and cancer vaccines, immunotherapy is emerging as a novel promising option for TNBC. This review is mainly focused on the tumour microenvironment and host immunity, Triple Negative Breast Cancer and the clinical treatment of TNBC, novel therapies for cancer and immunotherapy for TNBC, and the future outlook for the treatment for TNBC and the interplay between the therapies, including immune checkpoint inhibitors, combination of immune checkpoint inhibitors with targeted treatments in TNBC, adoptive cell therapy, cancer vaccines. The review also highlights recent reports on the synergistic effects of immunotherapy and chemotherapy, antibody–drug conjugates, and exosomes, as potential multifunctional therapeutic agents in TNBC.

Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.