Colorectal cancer (CRC) ranks as the second most prevalent malignancy globally, highlighting the urgent need for more effective diagnostic and therapeutic strategies, as well as a deeper understanding of its molecular basis. Extensive research has demonstrated that cells actively secrete extracellular vesicles (EVs) to mediate intercellular communication at both proximal and distal sites. In this study, we conducted a comprehensive analysis of the RNA content of small extracellular vesicles (sEVs) secreted into the culture media of five frequently utilised CRC cell lines (RKO, HCT116, HCT15, HT29, and DLD1). RNA sequencing data revealed significant insights into the RNA profiles of these sEVs, identifying nine protein-coding genes and fourteen long non-coding RNA (lncRNA) genes that consistently ranked among the top 30 most abundant across all cell lines. Notably, the genes found in sEVs were highly similar among the cell lines, indicating a conserved molecular signature. Several of these genes have been previously documented in the context of cancer biology, while others represent novel discoveries. These findings provide valuable insights into the molecular cargo of sEVs in CRC, potentially unveiling novel biomarkers and therapeutic targets.
- MeSH
- Extracellular Vesicles * metabolism genetics MeSH
- HCT116 Cells MeSH
- Colorectal Neoplasms * genetics pathology metabolism MeSH
- Humans MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Gene Expression Regulation, Neoplastic MeSH
- RNA, Long Noncoding genetics MeSH
- Sequence Analysis, RNA MeSH
- Gene Expression Profiling MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Breast cancer is a prevalent and aggressive disease characterized by high metastasis, recurrence, and mortality rates. While cisplatin is an effective chemotherapy drug, its use is limited by its toxic effects on the body. Despite advancements in therapeutic strategies, the therapeutic response is often unsatisfactory due to drug resistance, leading to poor prognosis. Recent studies have shown that cisplatin interacts with long non-coding RNAs (lncRNAs) and accelerates the development of resistance in tumor cells to therapy. This interaction highlights the complex mechanisms involved in the response of cancer cells to chemotherapy. Several lncRNAs have been identified as key players in mediating cisplatin resistance in breast cancer. These lncRNAs include SNHG15, HULC, HCP5, MT1JP, LncMat2B, DLX6-ASL, Linc00665, CARMN, and Lnc-EinRP44-3:6. These lncRNAs have been shown to target microRNAs and mRNAs and modulate the expression of genes involved in cisplatin resistance, which is important in treating breast cancer.
- MeSH
- Drug Resistance, Neoplasm * genetics MeSH
- Cisplatin * therapeutic use pharmacology MeSH
- Humans MeSH
- Breast Neoplasms * drug therapy genetics pathology metabolism MeSH
- Antineoplastic Agents * therapeutic use pharmacology MeSH
- Gene Expression Regulation, Neoplastic * drug effects MeSH
- RNA, Long Noncoding * genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Hepatocellular carcinoma (HCC) is primary liver cancer, frequently diagnosed at advanced stages with limited therapeutic options. MicroRNAs (miRNAs) regulate target gene expression and through inhibitory competitive binding of miRNA influence cellular processes including carcinogenesis. Extensive evidence proved that certain miRNA's are specifically expressed in neoplastic tissues of HCC patients and are confirmed as important factors that can participate in the regulation of key signalling pathways in cancer cells. As such, miRNAs have a great potential in the clinical diagnosis and treatment of HCC and can improve the limitations of standard diagnosis and treatment. Long non-coding RNAs (lncRNAs) have a critical role in the development and progression of HCC. HCC-related lncRNAs have been demonstrated to exhibit abnormal expression and contribute to transformation process (such as proliferation, apoptosis, accelerated vascular formation, and gain of invasive potential) through their interaction with DNA, RNA, or proteins. LncRNAs can bind mRNAs to release their target mRNA and enable its translation. These lncRNA-miRNA networks regulate cancer cell expression and so its proliferation, apoptosis, invasion, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and autophagy. In this narrative review, we focus on miRNA and lncRNA in HCC tumor tissue and their interaction as current tools, and biomarkers and therapeutic targets unravelled in recent years.
- Publication type
- Journal Article MeSH
- Review MeSH
The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers ?-smooth muscle actin and SM22? was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3'-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway. Keywords: Endothelial progenitor cells, Endothelial to mesenchymal transition, Linc-ROR, MiR-145, Atherosclerosis.
- MeSH
- Endothelial-Mesenchymal Transition MeSH
- Endothelial Progenitor Cells * metabolism MeSH
- Epithelial-Mesenchymal Transition * MeSH
- Cells, Cultured MeSH
- Humans MeSH
- MicroRNAs * metabolism genetics MeSH
- Cell Movement physiology MeSH
- Cell Proliferation MeSH
- Smad3 Protein * metabolism genetics MeSH
- RNA, Long Noncoding * genetics metabolism MeSH
- Signal Transduction * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease. OBJECTIVE: Evaluation of novel long non-coding RNAs biomarkers for breast cancer. METHODS: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics. RESULTS: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality. CONCLUSIONS: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.
- MeSH
- Adaptor Proteins, Signal Transducing genetics metabolism MeSH
- Adult MeSH
- Guanylate Kinases genetics metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * genetics metabolism MeSH
- Breast Neoplasms * genetics pathology metabolism mortality MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic MeSH
- RNA, Long Noncoding * genetics MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Genes, Tumor Suppressor MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.
- MeSH
- Extracellular Vesicles * metabolism MeSH
- RNA, Circular genetics metabolism MeSH
- Humans MeSH
- RNA, Messenger genetics metabolism MeSH
- Cell Communication MeSH
- MicroRNAs genetics metabolism MeSH
- Tumor Microenvironment * MeSH
- Neoplasms * pathology genetics metabolism MeSH
- RNA, Long Noncoding genetics MeSH
- RNA genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications.
- MeSH
- Biomarkers MeSH
- Extracellular Vesicles * genetics MeSH
- Colorectal Neoplasms * diagnosis genetics MeSH
- Humans MeSH
- RNA, Long Noncoding * genetics MeSH
- Neoplasms, Second Primary * MeSH
- Serum MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
- MeSH
- MicroRNAs * genetics MeSH
- RNA, Long Noncoding * genetics MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cervical squamous cell carcinoma (CSCC) represents a malignant subtype of cervical cancer. Identification of novel biomarkers for CSCC development could enhance therapeutic efficiency and improve the patients' outcomes. This study focused on lncRNA EMX2OS, evaluating its expression and significance in the progression of CSCC while exploring its potential as a therapeutic target. A cohort of 135 patients with CSCC were enrolled, and tissue samples were collected for analysis. The expression of EMX2OS in the tissues was quantified by PCR, with its correlation to the clinicopathological features, and prognosis was evaluated by χ2, Kaplan-Meier and Cox regression analyses. The regulatory effects of EMX2OS on CSCC cells were investigated by CCK8 and Transwell assays, while the underlying molecular mechanisms were elucidated by luciferase reporter assays. Significant down-regulation of EMX2OS was observed in CSCC, correlating with advanced FIGO stages, poor differentiation and adverse prognosis of patients. Over-expression of EMX2OS significantly suppressed cell growth and metastasis in CSCC. Negative regulation of miR-574-5p by EMX2OS was observed, and over-expression of miR-574-5p alleviated the inhibition of CSCC cells by EMX2OS. Down-regulated EMX2OS indicates severe disease progression and poor prognosis in CSCC. Over-expression of EMX2OS could inhibit CSCC cell growth and metastasis by negatively modulating miR-574-5p.
- MeSH
- Down-Regulation * genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs * genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Uterine Cervical Neoplasms * genetics pathology metabolism MeSH
- Prognosis MeSH
- Disease Progression * MeSH
- Cell Proliferation genetics MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- RNA, Long Noncoding * genetics metabolism MeSH
- Carcinoma, Squamous Cell * genetics pathology metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Renal cell carcinoma (RCC), a prevalent form of renal malignancy, is distinguished by its proclivity for robust tumor proliferation and metastatic dissemination. Long non-coding RNAs (lncRNAs) have emerged as pivotal modulators of gene expression, exerting substantial influence over diverse biological processes, encompassing the intricate landscape of cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), an exemplar among lncRNAs, has been discovered to assume functional responsibilities within the context of RCC. The conspicuous expression of MALAT-1 in RCC cells has been closely linked to the advancement of tumors and an unfavorable prognosis. Experimental evidence has demonstrated the pronounced ability of MALAT-1 to stimulate RCC cell proliferation, migration, and invasion, thereby underscoring its active participation in facilitating the metastatic cascade. Furthermore, MALAT-1 has been implicated in orchestrating angiogenesis, an indispensable process for tumor expansion and metastatic dissemination, through its regulatory influence on pro-angiogenic factor expression. MALAT-1 has also been linked to the evasion of immune surveillance in RCC, as it can regulate the expression of immune checkpoint molecules and modulate the tumor microenvironment. Hence, the potential utility of MALAT-1 as a diagnostic and prognostic biomarker in RCC emerges, warranting further investigation and validation of its clinical significance. This comprehensive review provides an overview of the diverse functional roles exhibited by MALAT-1 in RCC.
- MeSH
- Carcinoma, Renal Cell * genetics pathology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Microenvironment genetics MeSH
- Kidney Neoplasms * genetics pathology MeSH
- Prognosis MeSH
- Cell Proliferation genetics MeSH
- RNA, Long Noncoding * genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
