Construction and validation of a prognostic model with RNA binding protein-related mRNAs for the HBV-related hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor clinical outcomes, and the infection of hepatitis B virus (HBV) is the leading cause of this disease. Mounting evidence shows that RNA binding proteins (RBPs) can modulate the progression of cancers. However, the functions and clinical implications of RBP-related mRNAs in HBV-related HCC remain largely unclear. Therefore, we aim to develop a prognostic model based on the RBP-related mRNAs for HBV-related HCC patients. Firstly, we identified 626 differentially expressed RBP-related mRNAs in the HBV-related HCC through the Pearson correlation analysis. Subsequently, the Kaplan-Meier survival, univariate, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses were used to construct a prognostic model comprised of five RBP-related mRNAs. Furthermore, the patients were categorized into the high- and low-risk groups by the prognostic model and the patients in the high-risk group had a poor prognosis. Additionally, the prognostic model was an independent predictor of prognosis, and the accuracy of the prognostic model was proved by the receiver operator characteristic (ROC) analysis. Furthermore, the functional enrichment analysis revealed that various cancer-promoting processes were enriched in the high-risk group. Taken together, our study may provide the HBV-related HCC biomarkers of prognosis to improve the clinical outcomes of patients.

Integrated Analysis of a Ferroptosis-Related LncRNA Signature for Evaluating the Prognosis of Patients with Colorectal Cancer.

LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. However, the functions and clinical implications of ferroptosis-associated lncRNAs in CRC remain largely unknown. We, herein, aim to construct a prognostic signature with ferroptosis-related lncRNAs for the prognostic estimation of CRC patients. Firstly, we identified the lncRNAs related to ferroptosis based on the RNA-Seq data of CRC from the TCGA database. The univariate and multivariate Cox analyses were then performed to establish a prognostic signature composed of eight ferroptosis-related lncRNAs (AL161729.4, AC010973.2, CCDC144NL-AS1, AC009549.1, LINC01857, AP003555.1, AC099850.3, and AC008494.3). Furthermore, we divided the CRC patients into high- and low-risk groups based on the signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that in the low-risk group (p = 3.31 × 10-11). Moreover, the patients in the high-risk groups had shorter recurrence-free survival (RFS) (p = 6.5 × 10-3) and disease-free survival (DFS) (p = 4.27 × 10-4), as well as higher tumor recurrence rate. Additionally, we found that the oncogenic pathways were enriched in the high-risk group, whereas the ferroptosis pathway that probably repressed CRC development was enriched in the low-risk group. In summary, our signature may provide a theoretical foundation for not only accurate judgment for prognosis but also evaluation for recurrence and metastasis in CRC patients.

Effect of digestion on bound phenolic content, antioxidant activity and hypoglycemic ability of insoluble dietary fibre from four Triticeae crops.

To assess the physiological functions of bound phenols in insoluble dietary fiber (IDF) from different Triticeae crops, bound phenols in IDF were extracted from wheat, triticale, barley and quinoa. In addition, model in vitro was established and used in evaluating the release of bound phenols and changes in their physiological functions after simulated digestion. Results showed that bound phenol content in IDF from Triticeae crops before digestion was higher than which during digestion, and its physiological functions were also better (p < .05). Moreover, barley extracted before digestion, its bound phenolic content in IDF was higher than those in other three Triticeae crops, besides,its bound phenol also showed better antioxidant ability. Before digestion, bound phenols in IDF from triticale showed the best hypoglycemic ability (the inhibition rate of α-glucosidase was 95%; the inhibition rate of α-amylase was 97%). In the simulated digestion model, the bound phenols were mainly released during the intestinal digestion stage, they showed better physiological functions than which released at the gastric digestion stage. The bound phenol content in triticale was higher and its physiological functions was better than those in the other crops. PRACTICAL APPLICATIONS: The results of this experiment showed that the release of bound phenols measured by chemical extraction (i.e., before digestion) was higher than that by simulated gastrointestinal digestion. Compared with the chemical extraction method, in vitro gastro-intestinal digestion simulates the pH value and enzyme environment of food in the human body gastrointestinal digestion process more effectively. This study can provide reference for selecting Triticeae crops feeding in the future. To be more precise, bound phenol content in the insoluble dietary fiber of barley was the highest before digestion. The bound phenol in the insoluble dietary fiber of triticale had the best hypoglycemic ability. The bound phenolic compounds are mainly released during intestinal digestion, and their physiological functions are better than that in gastric digestion.

Guidance of circular RNAs to proteins' behavior as binding partners.

Circular RNAs (circRNAs) are single-stranded and covalently closed back-splicing products of pre-mRNAs. They can be derived from exons, introns, or exons with intron retained between exons of transcripts, as well as antisense transcripts. CircRNAs have been reported to function as microRNA sponges, regulate gene transcription mediated by RNA polymerase II, and modulate the splicing or stability of mRNA. However, emerging studies demonstrate that they affect the behavior of proteins via direct interactions with them. Here, we summarize that by binding directly with proteins; circRNAs can facilitate their nuclear or cytoplasmic localizations, regulate their functions or stability, promote or inhibit the interactions between them, or influence the interactions between them and DNA. Furthermore, these circRNA-binding proteins contain transcription factors, RNA processing proteins, proteases, and some other RNA-binding proteins. As a consequence, circRNAs are involved in the regulation of multiple physiological or pathological processes, including tumorigenesis, atherosclerosis, wound repair, cardiac senescence, myocardial ischemia/reperfusion injury, and so forth. Nonetheless, it is worthwhile to further explore more types of proteins that interact with circRNAs, which would be helpful in revealing other unknown biological functions of circRNAs that guide the variation in behavior of cellular proteins.

Regulation of RNA decay and cellular function by 3'-5' exoribonuclease DIS3L2.

DIS3L2, in which mutations have been linked to Perlman syndrome, is an RNA-binding protein with 3'-5' exoribonuclease activity. It contains two CSD domains and one S1 domain, all of which are RNA-binding domains, and one RNB domain that is responsible for the exoribonuclease activity. The 3' polyuridine of RNA substrates can serve as a degradation signal for DIS3L2. Because DIS3L2 is predominantly localized in the cytoplasm, it can recognize, bind, and mediate the degradation of cytoplasmic uridylated RNA, including pre-microRNA, mature microRNA, mRNA, and some other non-coding RNAs. Therefore, DIS3L2 plays an important role in cytoplasmic RNA surveillance and decay. DIS3L2 is involved in multiple biological and physiological processes such as cell division, proliferation, differentiation, and apoptosis. Nonetheless, the function of DIS3L2, especially its association with cancer, remains largely unknown. We summarize here the RNA substrates degraded by DIS3L2 with its exonucleolytic activity, together with the corresponding biological functions it is implicated in. Furthermore, we discuss whether DIS3L2 can function independently of its 3'-5' exoribonuclease activity, as well as its potential tumor-suppressive or oncogenic roles during cancer progression.

Long non-coding RNAs involved in cancer metabolic reprogramming.

Metabolic reprogramming has now been accepted as a hallmark of cancer. Compared to normal cells, cancer cells exhibit different metabolic features, including increased glucose uptake, aerobic glycolysis, enhanced glutamine uptake and glutaminolysis, altered lipid metabolism, and so on. Cancer metabolic reprogramming, which supports excessive cell proliferation and growth, has been widely regulated by activation of oncogenes or loss of tumor suppressors. Here, we review that long non-coding RNAs (lncRNAs) can affect cancer metabolism by mutual regulation with oncogenes or tumor suppressors. Additionally, the interaction of lncRNAs with crucial transcription factors, metabolic enzymes or microRNAs can also effectively modulate the processes of cancer metabolism. LncRNAs-derived metabolism reprogramming allows cancer cells to maintain deregulated proliferation and withstand hostile microenvironment such as energy stress. Understanding the functions of lncRNAs in cancer metabolic reprogramming that contributes to carcinogenesis and cancer development may help to develop novel and effective strategies for cancer diagnosis, prognosis and treatment.

Aberrant Regulation of mRNA m6A Modification in Cancer Development.

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic messenger RNAs (mRNAs). The m6A modification in RNA can be catalyzed by methyltransferases, or removed by demethylases, which are termed m6A writers and erasers, respectively. Selective recognition and binding by distinct m6A reader proteins lead mRNA to divergent destinies. m6A has been reported to influence almost every stage of mRNA metabolism and to regulate multiple biological processes. Accumulating evidence strongly supports the correlation between aberrant cellular m6A level and cancer. We summarize here that deregulation of m6A modification, resulting from aberrant expression or function of m6A writers, erasers, readers or some other protein factors, is associated with carcinogenesis and cancer progression. Understanding the regulation and functional mechanism of mRNA m6A modification in cancer development may help in developing novel and efficient strategies for the diagnosis, prognosis and treatment of human cancers.

Hinokitiol, a natural tropolone derivative, offers neuroprotection from thromboembolic stroke in vivo.

Hinokitiol ( ß -thujaplicin), a tropolone-related compound found in the heartwood cupressaceous plants, is widely used in hair tonics, tooth pastes, cosmetics, and food as an antimicrobial agent. Increasing evidence has confirmed that hinokitiol exhibits anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, we have investigated the neuroprotective effect and mechanisms of hinokitiol in rats against middle cerebral artery occlusion (MCAO)-induced thromboembolic stroke. Treatment with hinokitiol (0.2 and 0.5 mg/kg; intraperitoneally) 30 min before MCAO dose dependently attenuated cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Intraperitoneal administration of hinokitiol significantly reduced infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increased expressions of hypoxia-inducible factor (HIF)-1 α , inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)- α , and active caspase-3 in ischemic regions. However, these expressions were obviously inhibited by hinokitiol (0.2 and 0.5 mg/kg) treatment. This study demonstrates for the first time that in addition to being originally considered as an agent against microbes and variety of cancers, hinokitiol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1 α , iNOS expression) and apoptosis (i.e., TNF- α , active caspase-3), resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, the therapeutic potential of hinokitiol may lead to novel role for treatment or prevention of ischemia/reperfusion injury-related disorders.