Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.

Preeclampsia is a major contributor to maternal and fetal morbidity and mortality. The disorder can be classified into early- and late-onset subtypes, both of which evolve in two stages. The first stage comprises the development of pre-clinical, utero-placental malperfusion. Early and late utero-placental malperfusion have different causes and time courses. Early-onset preeclampsia (20 % of cases) is driven by dysfunctional placentation in the first half of pregnancy. In late-onset preeclampsia (80 % of cases), malperfusion is a consequence of placental compression within the confines of a limited uterine cavity. In both subtypes, the malperfused placenta releases stress signals into the maternal circulation. These stress signals trigger onset of the clinical syndrome (the second stage). Small RNA molecules, which are implicated in cellular stress responses in general, may be involved at different stages. Micro RNAs contribute to abnormal trophoblast invasion, immune dysregulation, angiogenic imbalance, and syncytiotrophoblast-derived extracellular vesicle signalling in preeclampsia. Transfer RNA fragments are placental signals known to be specifically involved in cell stress responses. Disorder-specific differences in small nucleolar RNAs and piwi-interacting RNAs have also been reported. Here, we summarise key small RNA advances in preeclampsia pathogenesis. We propose that existing small RNA classifications are unhelpful and that non-biased assessment of RNA expression, incorporation of non-annotated molecules and consideration of chemical modifications to RNAs may be important in elucidating preeclampsia pathogenesis.

OBJECTIVE: Small nucleolar RNAs (snoRNAs) form clusters within the genome, representing a mysterious category of small non-coding RNAs. Research has demonstrated that aberrant snoRNAs can contribute to the development of various types of cancers. Recent studies have identified snoRNAs as potentially valuable biomarkers for the diagnosis or/and prognosis of cancers. However, there has been a lack of comprehensive reviews on prognostic and diagnostic snoRNAs across different types of cancers.
METHODS: We conducted a systematic search of various databases including Google Scholar, Medline, Cochrane, Scopus, PubMed, Embase, ScienceDirect, Ovid-Medline, Chinese National Knowledge Infrastructure, WanFang, and SinoMed with a time frame reception to December 30, 2022. A total of 49 relevant articles were included in our analysis, consisting of 21 articles focusing on diagnostic aspects and 41 articles focusing on prognostic aspects. Pooled odds ratio, 95% confidence intervals (CIs), and hazard ratio (HR) were utilized to evaluate clinical parameters and overall survival (OS), respectively.
RESULTS: The findings indicated that area under the curve, sensitivity, and specificity were 0.85, 75%, and 80% in cancer, respectively. There was a possibility that snoRNAs had a positive impact on the diagnosis (risk ratio, RR = 2.95, 95% CI: 2.75-3.16, P = 0.000) and OS (HR = 1) in cancer. Additionally, abnormally expressed snoRNAs were associated with a positive impact on OS time for chronic lymphocytic leukemia (HR: 0.88, 95%Cl: 0.69-1.11, P < 0.00001), colon adenocarcinoma (HR: 0.97, 95%Cl: 0.91-1.03, P < 0.0001), and ovarian cancer (HR: 0.98, 95%Cl: 0.98-0.99, P < 0.00001). However, dysregulated snoRNAs of colon cancer and colorectal cancer had a negative impact on OS time (HR = 3.01 and 1.01 respectively, P < 0.0001).
CONCLUSIONS: The results strongly suggested that snoRNAs could serve as potential novel indicators for prognosis and diagnosis in cancers. This systematic review followed the guidelines of the Transparent Reporting of Systematic Review and Meta-Analyses (PROSPERO register: CRD42020209096).

Small nucleolar RNA H/ACA Box 51 (SNORA51) is involved in progression of multiple cancers. However, its role in hepatocellular carcinoma (HCC) is still unclear. The aim of the present study was to analyze the expression of SNORA51 in HCC and its clinical significance. A total of 136 patients with HCC who underwent surgery from January 1, 2016 to December 31, 2018 were included. The expression of SNORA51 in cancer tissues and adjacent tissues was compared using reverse transcription-quantitative PCR and bioinformatics methods. Methylation of the SNORA51 promoter in cancer and adjacent tissues was compared using bioinformatics. The relationship between SNORA51 expression levels and clinicopathological characteristics of patients with HCC, in addition to prognosis, was analyzed. The expression of SNORA51 in HCC was significantly higher compared with that in adjacent tissues (P<0.05). starBase demonstrated that higher expression levels of SNORA51 were associated with a significantly worse prognosis of patients with HCC compared with those who had lower expression levels of SNORA51 (P<0.05). Bioinformatics analysis using The University of Alabama at Birmingham Cancer Data Analysis Portal demonstrated that methylation of the SNORA51 promoter region in HCC was significantly decreased compared with adjacent tissues (P<0.05). A high expression of SNORA51 was significantly associated with portal vein tumor thrombus, vascular invasion and TNM stage (P<0.05). The median survival time of patients with high SNORA51 expression was significantly lower compared with those who had low SNORA51 expression (P<0.05). Both uni- and multivariate Cox regression analysis demonstrated that SNORA51 expression was an independent risk factor that significantly worsened the prognosis of patients with HCC (P<0.05). The overexpression of SNORA51 in patients with HCC was significantly associated with a poor prognosis and may be related to the reduced methylation of the SNORA51 promoter region. Therefore, SNORA51 may be a promising biomarker for prediction of the prognosis of patients with HCC and may be a therapeutic target for the treatment of HCC in future.

Introduction: The anterior cruciate ligament (ACL) is susceptible to degeneration, resulting in joint pain, reduced mobility, and osteoarthritis development. There is currently a paucity of knowledge on how anterior cruciate ligament degeneration and disease leads to osteoarthritis. Small non-coding RNAs (sncRNAs), such as microRNAs and small nucleolar RNA (snoRNA), have diverse roles, including regulation of gene expression. Methods: We profiled the sncRNAs of diseased osteoarthritic ACLs to provide novel insights into osteoarthritis development. Small RNA sequencing from the ACLs of non- or end-stage human osteoarthritic knee joints was performed. Significantly differentially expressed sncRNAs were defined, and bioinformatics analysis was undertaken. Results and Discussion: A total of 184 sncRNAs were differentially expressed: 68 small nucleolar RNAs, 26 small nuclear RNAs (snRNAs), and 90 microRNAs. We identified both novel and recognized (miR-206, -365, and -29b and -29c) osteoarthritis-related microRNAs and other sncRNAs (including SNORD72, SNORD113, and SNORD114). Significant pathway enrichment of differentially expressed miRNAs includes differentiation of the muscle, inflammation, proliferation of chondrocytes, and fibrosis. Putative mRNAs of the microRNA target genes were associated with the canonical pathways \"hepatic fibrosis signaling\" and \"osteoarthritis.\" The establishing sncRNA signatures of ACL disease during osteoarthritis could serve as novel biomarkers and potential therapeutic targets in ACL degeneration and osteoarthritis development.

Non-coding RNAs (ncRNAs) are abundant single-stranded RNA molecules in human cells, involved in various cellular processes ranging from DNA replication and mRNA translation regulation to genome stability defense. MicroRNAs are multifunctional ncRNA molecules of 18-24 nt in length, involved in gene silencing through base-pair complementary binding to target mRNA transcripts. piwi-interacting RNAs are an animal-specific class of small ncRNAs sized 26-31 nt, responsible for the defense of genome stability via the epigenetic and post-transcriptional silencing of transposable elements. Long non-coding RNAs are ncRNA molecules defined as transcripts of more than 200 nucleotides, their function depending on localization, and varying from the regulation of cell differentiation and development to the regulation of telomere-specific heterochromatin modifications. The current review provides recent data on the several forms of small and long non-coding RNA\'s potential to act as diagnostic, prognostic or therapeutic target for various human diseases.

Small Nucleolar RNAs (snoRNAs) are an abundant group of non-coding RNAs with well-defined roles in ribosomal RNA processing, folding and chemical modification. Besides their classic roles in ribosome biogenesis, snoRNAs are also implicated in several other cellular activities including regulation of splicing, transcription, RNA editing, cellular trafficking, and miRNA-like functions. Mature snoRNAs must undergo a series of processing steps tightly regulated by transiently associating factors and coordinated with other cellular processes including transcription and splicing. In addition to their mature forms, snoRNAs can contribute to gene expression regulation through their derivatives and degradation products. Here, we review the current knowledge on mechanisms of snoRNA maturation, including the different pathways of processing, and the regulatory mechanisms that control snoRNA levels and complex assembly. We also discuss the significance of studying snoRNA maturation, highlight the gaps in the current knowledge and suggest directions for future research in this area.

Cancer is a major health hazard for humans. Recent studies have indicated the involvement of small nucleolar RNAs (snoRNAs) in the occurrence and development of cancer and indicated its potential role as a diagnostic/prognostic marker and therapeutic target. The purpose of this study was to use the bibliometrics method to analyze the published literature on this subject. We collected articles pertaining to the field of snoRNA and cancer from the Web of Science Core Collection database. The data were analyzed to identify the research hotspots and frontiers. The number of articles in this field was low in the early period. Chu Liang and Montanaro Lorenzo were the most prolific authors on this subject, while Jiang and Feng were the most frequently cited authors. In China, three institutions published the most articles, namely Wuhan Univ, China Med Univ, and Guangxi Med Univ. The journal with the highest number of articles on this subject was Oncotarget. The country with the most published articles was China. Analysis of keywords and burst words indicated that early studies mainly focused on molecular mechanisms. Available evidence suggests the involvement of snoRNAs in the molecular mechanism of cancer development and their potential role as a diagnostic and prognostic biomarker.

Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.

Hepatoblastoma (HB) is a common pediatric malignant liver tumor that is characterized by a low level of genetic mutations. Alternative splicing (AS) has been shown to be closely associated with cancer progression, especially in tumors with a low mutational burden. However, the role of AS in HB remains unknown.
Transcriptome sequencing was performed on 5 pairs of HB tissues and matched non-tumor tissues to delineate the AS landscape in HB. AS events were validated in 92 samples from 46 patients. RNA pull-down and RNA immunoprecipitation assays were carried out to identify splicing factors that regulate the AS of small nucleolar RNA host genes (SNHG). Patient-derived organoids (PDOs) were established to investigate the role of the splicing factor polyadenylate-binding nuclear protein 1 (PABPN1).
This study uncovered aberrant alternative splicing in HB, including lncRNAs from SNHG family that undergo intron retention in HB. Further investigations revealed that PABPN1, a significantly upregulated RNA binding protein, interacts with splicing machinery in HB, inducing the intron retention of these SNHG RNAs and the downregulation of intronic small nucleolar RNAs (snoRNAs). Functionally, PABPN1 acts as an oncofetal splicing regulator in HB by promoting cell proliferation and DNA damage repair via inducing the intron retention of SNHG19. Knock-down of PABPN1 increases the cisplatin sensitivity of HB PDOs.
Our findings revealed the role of intron retention in regulating snoRNA expression in hepatoblastoma, explained detailed regulatory mechanism between PABPN1 and the intron retention of SNHG RNAs, and provided insight into the development of new HB treatment options.