non-coding rna

Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA types, have emerged as key regulators in neurodegenerative diseases and brain tumors. This review aims to provide insights into the role of ncRNAs in these conditions and their potential as diagnostic and therapeutic targets. We systematically reviewed literature from databases such as PubMed, Scopus, and Web of Science, applying specific inclusion and exclusion criteria to ensure comprehensive coverage of recent advancements. Although ncRNAs are involved in a range of molecular pathways, challenges in clinical translation, including specificity, cost, and validation, persist. This review highlights innovative strategies to overcome these barriers and promote the clinical application of ncRNAs. Moreover, we explore the emerging role of extracellular vesicle-enriched ncRNAs as cell-free therapeutic options for neurodegenerative diseases. The findings presented here emphasize the need for robust validation and the development of specific ncRNA-based treatments.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal malignancies globally. Non-coding RNAs (ncRNAs) are pivotal in regulating gene expression and cancer progression, yet their precise functions within HCC pathways remain elucidated.

To investigate the role of ncRNAs in regulating key genes involved in Hippo signaling and HCC pathways and to identify potential novel regulatory mechanisms in HCC progression.

Gene expression data from the GEO database (GSE14520) were analyzed for expression changes of LEF1, MOB1A, PRKCB, and SMARCA2 in HCC. Physical interactions between selected ncRNAs (lnc-LRR1-1:1, lnc-LRR1-1:2, and hsa_circ_0001380) and target mRNAs were predicted, using the long non-coding RNA-target analysis resource (LncTAR) tool. miRNA analysis was performed to identify potential competing endogenous RNA (ceRNA) mechanisms. qPCR analysis in HCC cell lines was conducted for experimental validation.

Significant upregulation of LEF1 and downregulation of PRKCB were observed in HCC samples. The strongest predicted interactions were identified between lnc-LRR1-1:2 and MOB1A isoforms. miRNA analysis suggested that the studied ncRNAs could act as ceRNAs. qPCR analysis confirmed upregulation of hsa_circ_0001380 and slight downregulation of lnc-LRR1-1:1,2 in HCC cell lines.

This study unveils a complex regulatory network, where ncRNAs can modulate the expression of key genes in HCC. The predicted interactions, particularly between lnc-LRR1-1:2 and MOB1A, and between hsa_circ_0001380 and hsa-miR-193b-3p suggest novel regulatory mechanisms in HCC progression. These findings provide new insights into the role of ncRNAs in HCC pathogenesis and identify potential avenues for future research and targeted therapies.

Colorectal cancer (CRC) is a common malignancy with high mortality. Despite advancements in understanding its molecular causes and improved drug therapies, patient survival rates remain low. The main reasons for the high mortality rate are cancer metastasis and the emergence of drug-resistant cancer cell populations. While genetic changes are recognized as the main driver of CRC occurrence and progression, recent studies suggest that epigenetic regulation is a crucial marker in cancer, influencing the interplay between genetics and the environment. Research has shown the significant regulatory roles of non-coding RNAs (ncRNAs) in CRC development. This review explores epigenetically regulated ncRNAs and their functions, aiming to understand key regulatory mechanisms that impact CRC development. Additionally, it discusses the potential use of these ncRNAs in CRC diagnosis, prognosis, and targeted treatments.

Gastric cancer has become the leading type of cancer on an international scale, with metastatic cancer being the leading cause of mortality associated with this illness. Consequently, methods for early detection have been established, mainly through the use of non-invasive biomarkers present in different bodily fluids. Exosomes are distinct extracellular vehicles that transport cellular signals over long distances via diverse contents. They may be readily seen in bodily fluids due to their secretion by gastric cancer cells or cells in the gastric cancer-tumor microenvironment. Given this context, multiple biological and functional features of human tumors, especially gastric cancer, are intricately connected to exosomal non-coding RNAs (ncRNAs). Exosomal microRNAs play a crucial role in several stages of gastric cancer progression, facilitating the transfer of genetic information between cancer cells and other cells. This process regulates tumor angiogenesis, growth, metastasis, immunological responses, and medication resistance. They engage with several regulatory complexes that have different enzymatic activities. These complexes then alter the chromatin landscapes, including changes to nucleosomes, DNA methylation, and alterations to histones. This research delves into the essential regulatory mechanisms of exosomes in gastric cancer. Furthermore, the existing understanding of the functions of exosomal miRNAs in this context was evaluated, aiming to confirm their potential significance in identifying biomarkers, elucidating their roles in immune evasion and drug resistance, and ultimately evaluating therapeutic strategies.

Multiple myeloma (MM) drug resistance is thought to be caused by the development of protective autophagy. This work aimed to assess the non-coding RNA (ncRNA) autophagy-related alterations in drug-resistant (DR) myeloma cells.

DR Plasma cells were extracted from the bone marrow of DR patients referred to Baghai 2 Hospital in Ahvaz, Iran. The cells were grown in RPMI-1640 media containing 10% FBS and 1% Pen/Strep and incubated at 37˚C and 5% CO2. After six passages, the plasma cells were precisely isolated and utilized as DR cells. The U266B1 cell line (IBRC C10148) was grown in the RPMI-1640 media containing 10% FBS and 1% Pen/Strep and utilized as drug-sensitive (DS) cells. The relative expression of the genes was determined using the Real-time PCR method. Statistical analysis of the data was performed using GraphPad Prism 8 software.  

When the DR cells were compared to the DS cells, there was a notable increase in the expression of ULK1 and LC3B. However, expression of P62 in the DR plasma cells showed a significant decrease compared to the DS plasma cells. The miR-1297 level was considerably higher in the DR cells than in the DS cells. Although, there was no statistically significant difference in the expression of miR-26a-5p between the DS and DR cells. The DR cells exhibited a statistically significant increase in the expression of MALAT1 and SNHG6.

Drug resistance in MM cells may result from overexpression of non-coding RNAs involved in autophagy.

We aimed to investigate  miR-21-5p inhibition effect on lncRNA-XIST expression and apoptosis status of MCF-7 cells.

The MCF-7 cells were cultured and transfected by the anti-miR-21-5p oligonucleotide and expression of miR-21-5p, lncRNA-XIST, apoptosis-associated genes (bax and p53) and one miR-21-5p-unrelated lncRNA (BC200) was assessed by RT-qPCR. Furthermore, cell viability checked by MTT assay and apoptosis and cell cycle in transfected cells were detected by flow cytometry. Also, bioinformatics analysis on the transcriptome data confirmed that the lncRNA XIST might have a critical role in breast cancer (BC) cell apoptosis through ceRNAs mechanism and possible regulatory interactions with miR-21-5p.

Expression of miR-21-5p and lncRNA-XIST was significantly down- and up-regulated respectively (P<0.05). However, there was no significant change in lncRNA-BC200 expression. Also, the expression of bax and p53 upraised significantly (P<0.05). In transfected cells, MTT and flow cytometry assays reported a highly significant decrease and increase in viability and apoptosis respectively.

Inhibition of miR-21-5p resulted in significant upregulation of lncRNA-XIST and apoptosis-associated genes bax and p53, which led to the induction of apoptosis in MCF-7 cells. Therefore, more investigations may provide a valuable target for studies on molecular therapies for BC.

Coronary artery disease (CAD) and its numerous consequences significantly reduce the quality of life for millions of people worldwide.

This study investigated the differential expression of let-7 microRNA between CAD patients and healthy peers, which can be used as an early diagnostic, therapeutic, and preventive tool.

In this case-control study, participants were selected through convenient sampling and categorized into CAD-positive (n = 25) and CAD-negative (n = 25) groups. Blood samples were obtained, and the level of let-7 miRNA was measured. Various other parameters, including demographic variables, blood pressure, and results of routine blood tests besides smoking status, educational level, overweight, diabetes status, and history of coronary atherosclerosis, were recorded. Familial history of hypertension, diabetes, atherosclerosis, and sudden death were also registered. Different statistical methods including independent sample t, Mann-Whitney, and chi-squared tests were used to compare variables. A P value of less than 0.05 was considered significant.

Patients with CAD were older, with a higher frequency of the male sex. Fasting blood sugar (P = 0.002), triglyceride (P < 0.001), HDL-cholesterol (P = 0.038), triglycerideglucose index (P < 0.001), TG/HDL-cholesterol ratio (P < 0.001), and LDL/HDL ratio (P = 0.011) were significantly higher in the case group. Also, smoking (P = 0.001), illiteracy (P = 0.005), dyslipidemia (P = 0.048), and a history of coronary atherosclerosis (P = 0.022) were more prevalent in the CAD patients. Differential expression of let-7 microRNA between groups was at the borderline of statistical significance (P = 0.058).

Let-7 microRNA was expressed higher in patients with CAD, which may be helpful in the early diagnosis of atherosclerotic plaques and can possibly be used in designing therapeutic and preventive approaches.

The main role of ncRNAs (non-coding RNAs) is to regulate various cellular activities. LncRNAs (long non-coding RNAs) are a group of ncRNAs that are over 200 base pairs in length. It has been shown that lncRNAs regulate and control various cellular functions. Disruption of the expression of lncRNAs can cause various disease and deficiency in the cell function. LncRNA-HULK is one of lncRNA, which is greatly increased in liver disorders, including hepatitis C. Recently, the use of HULK as a biomarker has been suggested as a prognostic factor for liver disease such as hepatocellular carcinoma. Therefore, this study aimed to investigate the level of lncRNA-Hulk in chronic HCV-infected patients.

The present study included 50 patients with chronic hepatitis C. After transferring the samples, total RNA was extracted and the quantity of HCV-RNA and lncRNA-HULK were determined using the real-time PCR assay. Finally, the relationship between HCV-RNA and lncRNA-HULK levels was evaluated.

Of the total patients, 13 were female and 37 were male. All patients were HIV Ag/Ab and HBs Ag negative. Results showed that HCV-RNA level was 4,500-2,300,000 copies per mL of plasma. In addition, threshold cycles of lncRNA-HULK were calculated 28-38. Statistical analyses showed that there was a significant relationship between HCV-RNA level and lncRNA-HULK in the plasma of chronic patients.

In the recent study, the relationship between HCV-RNA quantity and lncRNA-HULC level in chronic hepatitis C patients was investigated. It is suggested that lncRNA-HULC levels could be considered as a biomarker in such patients. Accordingly, lncRNA-HULC quantification could be utilized to predict the progression of liver disease and the outcome in chronic HCV-infected patients.

Endometrial cancer is the fourth most widespread cancer among females, with a growing prevalence in recent years. Management by combined therapies along with surgery, radiotherapy, and chemotherapy have improved patients’ prognoses. Besides, the development of new therapies helps preserve fertility and prognosis in aggressive tumors.The purpose of this research was to identify the efficacy of metformin on the H19 long non-coding RNA expression in endometrial cancer to provide further insight into the pathogenesis and treatment of the disease.

A total of 23 patients with endometrial cancer, diagnosed by biopsy or diagnostic curettage, were recruited and divided into three groups, before and after metformin treatment and placebo. Real-time PCR was used to evaluate the H19 expression in cancer tissue in all patients.

It has been observed that in endometrial tissue of the “after-metformin” treatment group, the H19 expression level was significantly reduced, compared with the “before-metformin” treatment group, but not in comparison with the placebo. These findings indicate that metformin reduced the H19 expression in endometrial cancer.

Anti-diabetic drugs, such as metformin, may be beneficial by reducing the H19 expression in endometrial cancer due to the H19 relation to cancer progression.

Large intergenic non-coding RNA regulator of reprogramming (LINC-ROR), as a cancer-related Long non-coding RNA, has vital roles in stem cell survival, pluripotency, differentiation, and self-renewal in human embryonic stem cell. However, cancer-related molecular mech anisms, its functional roles, and clinical value of LINC-ROR in gastric cancer (GC) remain unclear. In this study, we aimed to investigate probable interplay between LINC-ROR with SALL4 stemness regulator and their role with the development of the disease.

The mRNA expression profile of LINC-ROR and SALL4 was assessed in tumoral and adjacent non-cancerous tissues of GC patients, using quantitative real-time PCR.

Significant LINC-ROR underexpression and SALL4 overexpression were observed in 55.81% and 75.58% (p < 0.0001) of samples, respectively. The expression of LINC-ROR and SALL4 were significantly correlated with each other (p = 0.044). There was an association between the underexpression of LINC-ROR and sex, stage of tumor progression, tumor type, and location of tumor (p < 0.05), and Helicobacter pylori infection with SALL4 expression (p = 0.036). There were also significant correlations between concomitant mRNA expression of SALL4 and LINC-ROR in tumors located at distal noncardiac, positive for H. pylori infection, tumors with invasion into the muscle layer of the stomach, and grade II tumor (p < 0.05). 

The clinical results of the SALL4-LINC-ROR association propose a probable functional interaction between these markers in tumor maintenance and aggressiveness. Our study can help to understand one of the mechanisms involved in the progression of gastric cancer through the function of these regulators.

Riboswitches are special non-coding sequences usually located in mRNAs’ un-translated regions and regulate gene expression and consequently cellular function. Furthermore, their interaction with antibiotics has been recently implicated. This raises more interest in development of bioinformatics tools for riboswitch studies. Herein, we describe the development and employment of novel block location-based feature extraction (BLBFE) method for classification of riboswitches.

We have already developed and reported a sequential block finding (SBF) algorithm which, without operating alignment methods, identifies family specific sequential blocks for riboswitch families. Herein, we employed this algorithm for 7 riboswitch families including lysine, cobalamin, glycine, SAM-alpha, SAM-IV, cyclic-di-GMP-I and SAH. Then the study was extended toward implementation of BLBFE method for feature extraction. The outcome features were applied in various classifiers including linear discriminant analysis (LDA), probabilistic neural network (PNN), decision tree and k-nearest neighbors (KNN) classifiers for classification of the riboswitch families. The performance of the classifiers was investigated according to performance measures such as correct classification rate (CCR), accuracy, sensitivity, specificity and f-score.

As a result, average CCR for classification of riboswitches was 87.87%. Furthermore, application of BLBFE method in 4 classifiers displayed average accuracies of 93.98% to 96.1%, average sensitivities of 76.76% to 83.61%, average specificities of 96.53% to 97.69% and average f-scores of 74.9% to 81.91%.

Our results approved that the proposed method of feature extraction; i.e. BLBFE method; can be successfully used for classification and discrimination of the riboswitch families with high CCR, accuracy, sensitivity, specificity and f-score values.