Ribosomal RNA Pseudouridylation: Will Newly Available Methods Finally Define the Contribution of This Modification to Human Ribosome Plasticity?

In human rRNA, at least 104 specific uridine residues are modified to pseudouridine. Many of these pseudouridylation sites are located within functionally important ribosomal domains and can influence ribosomal functional features. Until recently, available methods failed to reliably quantify the level of modification at each specific rRNA site. Therefore, information obtained so far only partially explained the degree of regulation of pseudouridylation in different physiological and pathological conditions. In this focused review, we provide a summary of the methods that are now available for the study of rRNA pseudouridylation, discussing the perspectives that newly developed approaches are offering.

Platelets' RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules.

BACKGROUND & AIMS: Among the multiplicity of factors involved in rising incidence of hepatocellular carcinoma (HCC)-the second deadliest cancer, late diagnosis of early-stage HCC nodules originating from late-stage cirrhotic nodules is the most crucial. In recent years, Tumor-educated platelets (TEPs) have emerged as a strong multimodal tool to be used in liquid-biopsy of cancers because of changes in their mRNA content. This study assessed the reliability of selected mRNA repertoire of platelets as biomarkers to differentiate early HCC from late-stage cirrhotic nodules. METHODS: Quantitative real time PCR (qRT-PCR) was used to evaluate expression levels of selected platelets-specific mRNA between HCC patients compared to cirrhosis patients. ROC curve analysis assessed the sensitivity and specificity of the biomarkers. RESULTS: RhoA, CTNNB1 and SPINK1 showed a significant 3.3-, 3.2- and 3.18-folds upregulation, respectively, in HCC patients compared to cirrhosis patients while IFITM3 and SERPIND1 presented a 2.24-fold change. Strikingly, CD41+ platelets also demonstrated a marked difference of expression in HCC and cirrhosis groups. CONCLUSIONS: Our study reports liquid biopsy-based platelets mRNA signature for early diagnosis of HCC from underlying cirrhotic nodules. Moreover, differential expression of CD41+ platelets in two groups provides new insights into a probable link between CD41 expression on platelets with the progression of cirrhosis to HCC.

Tumor educated platelets, a promising source for early detection of hepatocellular carcinoma: Liquid biopsy an alternative approach to tissue biopsy.

PURPOSE: Liver cancer is considered to be the sixth deadliest cancer worldwide. Hepatocellular carcinoma (HCC) is known to be the most prevalent type of liver cancer. The number of deaths due to HCC reported per year is on a constant rise especially in lesser developed countries. There are several contributing factors to this rise in number. Among other contributing factors is the late diagnosis of HCC. Patients are usually diagnosed when the disease reaches its advance stage. The present study was conducted with total 30 samples. It was designed for investigating the potential of TGF-ß, NF-κß, VEGF, AKT and PI3K as RNA based biomarkers in tumor educated platelets for early detection of HCC. RESULTS: The results obtained from the transcriptional analysis revealed a significant high expression of TGF-ß, NF-κß, VEGF by 2.48, 2.35 and 2.78 folds respectively in comparison to the control. On the other hand, a decrease in expression by 0.6 and 0.65 folds was observed in AKT and PI3K respectively in comparison to controls. Although all selected RNA biomarkers showed promising potential to detect HCC however, AKT and PI3K were better able to detect early stage HCC. CONCLUSIONS: The results obtained clearly indicate the increased expression of TGF-ß, NF-κß, VEGF in HCC patients. All these biomarkers are previously known for cancer initiation, progression and metastasis. The significant decrease in expression of AKT and PI3K in HCC patients needs further investigation. All the selected RNA biomarkers can be used for detection of HCC as they were able to distinguish HCC patients from controls successfully with AKT and PI3K showing better potential to detect early stage HCC. However, translational analysis for all these RNA biomarkers should be performed to gain further evidence for the ability of these biomarkers to be used for early HCC detection.

Multifaceted role of cancer educated platelets in survival of cancer cells.

Platelets, the derivatives of megakaryocytes, pose dynamic biological functions such as homeostasis and wound healing. The mechanisms involved in these processes are utilized by cancerous cells for proliferation and metastasis. Platelets through their activation establish an aggregate termed as Tumor cell induced platelet aggregation (TCIPA) that aids in establishing a niche for the primary tumor at secondary site while recruiting granulocytes and monocytes. The study of these close interactions between the tumor and the platelets can be exploited as biomarkers in liquid biopsy for early cancer detection, thereby increasing the life expectancy of cancer patients.