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Cancer is a complex genetic disorder characterized by abnormalities in both coding and regulatory non-coding RNAs. microRNAs (miRNAs) are key regulatory non-coding RNAs that modulate cancer development, functioning as both tumor suppressors and oncogenes. miRNAs play critical roles in cancer progression, influencing key processes such as initiation, promotion, and metastasis. They exert their effects by targeting tumor suppressor genes, thereby facilitating cancer progression, while also inhibiting oncogenes to prevent further disease advancement. The miR-10 family, particularly miR-10a-5p and miR-10b-5p (miR-10a/b-5p), is notably involved in cancer progression. Intriguingly, their functions can differ across different cancers, sometimes promoting and at other times suppressing tumor growth depending on the cancer type and target genes. This review explores the dual roles of miR-10a/b-5p as tumor-suppressive miRNAs (TSmiRs) or oncogenic miRNAs (oncomiRs) in various cancers by examining their molecular and cellular mechanisms and their impact on the tumor microenvironment. Furthermore, we discuss the potential of miR-10a/b-5p as therapeutic targets, emphasizing miRNA-based strategies for cancer treatment. The insights discussed in this review aim to advance our understanding of miR-10a/b-5p’s roles in tumor biology and their application in developing innovative cancer therapies.

The aim of this study was to identify and evaluate microRNAs (miRNAs) in gastric cancer lymph node metastasis. A miRNA array was used to compare the expression of miRNAs in primary gastric cancer and paired lymph node metastases. miRNAs found to be differentially expressed were validated in a cohort of primary gastric cancer tissues, and the relationship between expression and the clinicopathological characteristics of the specimens was analyzed. The expression level of miR-10a in a gastric mucosal cell line and three gastric cancer cell lines was also detected using qPCR. Moreover, the target genes for miR-10a were predicted using bioinformatic methods. Based on the results, four differentially expressed miRNAs were detected by the miRNA array. Compared with primary gastric cancer, lymph node metastases displayed downregulated expression of miR-24-1*, miR-510 and miR-1284, while the expression of miR-10a was upregulated. Consequently, analysis found that the expression of miR-10a was associated with lymph node metastasis (P=0.047), but was independent of the state of lymphatic invasion (P=0.169) in the cohort of primary gastric carcinoma. The expression of miR-10a was at least 10-fold higher in the three gastric cancer cell lines than in the gastric mucosal cell line. Two gastric cancer cell lines, which were established from lymph node metastasis, expressed higher miR-10a compared to the primary tumor origin cell line. Bioinformatic analysis demonstrated that the target genes of miR-10a are involved in multiple related pathways of tumorigenesis and metastasis. In conclusion, our study suggests that miR-10a is involved in the development of gastric cancer and lymph node metastasis, particularly in the latter process.

Background Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells. Results In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage. Conclusions This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage

Background Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes. Although abnormalities in cytokine signaling are common in MPN, the pathophysiology of atypical MPN still remains elusive. Since deregulation of microRNAs is involved in the biology of various cancers, we studied the miRNome of aMPN patients. Methods MiRNome and mutations in epigenetic regulator genes ASXL1, TET2, DNMT3A, EZH2 and IDH1/2 were explored in aMPN patients. Epigenetic regulation of miR-10a and HOXB4 expression was investigated by treating hematopoietic cell lines with 5-aza-2’deoxycytidine, valproic acid and retinoic acid. Functional effects of miR-10a overexpression on cell proliferation, differentiation and self-renewal were studied by transducing CD34+ cells with lentiviral vectors encoding the pri-miR-10a precursor. Results MiR-10a was identified as the most significantly up-regulated microRNA in aMPN. MiR-10a expression correlated with that of HOXB4, sitting in the same genomic locus. The transcription of these two genes was increased by DNA demethylation and histone acetylation, both necessary for optimal expression induction by retinoic acid. Moreover, miR-10a and HOXB4 overexpression seemed associated with DNMT3A mutation in hematological malignancies. However, overexpression of miR-10a had no effect on proliferation, differentiation or self-renewal of normal hematopoietic progenitors. Conclusions MiR-10a and HOXB4 are overexpressed in aMPN. This overexpression seems to be the result of abnormalities in epigenetic regulation mechanisms. Our data suggest that miR-10a could represent a simple marker of transcription at this genomic locus including HOXB4, widely recognized as involved in stem cell expansion.

Long non-coding RNA (lncRNA) is associated with a large number of tumor cellular functions together with chemotherapy resistance in a variety of tumors. LINC00963 was identified to regulate the malignant progression of various cancers. However, whether LINC00963 affects drug resistence in esophageal squamous cell carcinoma (ESCC) and the relevant molecular mechanisms have never been reported. This study aims to investigate the effect of LINC00963 on cisplatin resistance in ESCC. After detecting the level of LINC00963 in human esophageal squamous epithelial cells (HET-1 A), ESCC cells (TE-1) and cisplatin resistant cells of ESCC (TE-1/DDP), TE-1/DDP cell line and nude mouse model that interfered with LINC00963 expression were established. Then, the interaction among LINC00963, miR-10a, and SKA1 was clarified by double luciferase and RNA immunoprecipitation (RIP) assays. Meanwhile, the biological behavior changes of TE-1/DDP cells with miR-10a overexpression or SKA1 silencing were observed by CCK-8, flow cytometry, scratch, Transwell, and colony formation tests. Finally, the biological function of the LINC00963/SKA1 axis was elucidated by rescue experiments. LINC00963 was upregulated in TE-1 and TE-1/DDP cell lines. LINC00963 knockdown inhibited SKA1 expression of both cells and impaired tumorigenicity. Moreover, LINC00963 has a target relationship with miR-10a, and SKA1 is a target gene of miR-10a. MiR-10a overexpression or SKA1 silencing decreased the biological activity of TE-1/DDP cells and the expression of SKA1. Furthermore, SKA1 overexpression reverses the promoting effect of LINC00963 on cisplatin resistance of ESCC. LINC00963 regulates TE-1/DDP cells bioactivity and mediates cisplatin resistance through interacting with miR-10a and upregulating SKA1 expression.

A series of differentially expressed circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were identified through sequencing in the hair follicle tissues of Hu sheep with small-waved and straight wool patterns. Based on these findings, the circCSPP1-miR-10a-BMP7 (Bone Morphogenetic Protein 7) regulatory network was constructed. The preliminary study highlighted that miR-10a and the BMP7 gene exhibited not only significant differential expression across hair follicle tissues with different patterns in Hu sheep but also had an impact on the proliferation of hair papilla cells. The proliferation of hair papilla cells is intricately linked to hair follicle development and growth. Consequently, we selected the circCSPP1-miR-10a-BMP7 regulatory network to validate its role in promoting hair papilla cell proliferation in Hu sheep. Firstly, the authenticity of circCSPP1 was successfully confirmed through RNase R digestion and reverse primer amplification. Additionally, nucleoplasmic localization analysis determined that circCSPP1 was predominantly distributed in the cytoplasm. Using the dual-luciferase gene reporter system, we verified the targeting relationship between circCSPP1 and miR-10a, building upon our previous validation of the miR-10a-BMP7 interaction. This clarified the competing endogenous RNA (ceRNA) mechanism within the circCSPP1-miR-10a-BMP7. Furthermore, rescue experiments confirmed that circCSPP1 competitively binds to miR-10a, thereby regulating BMP7 expression and influencing the proliferation of hair papilla cells in Hu sheep. This discovery provides a solid foundation for future investigations into the mechanisms underlying wool curvature and the formation of lambskin patterns, offering insights into the complex regulatory networks that govern these phenotypic traits in Hu sheep.

Background： MicroRNAs （miRNAs） have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration. Methods： The Sprague-Dawley male rats were assigned to 70% partially hepatectomized group （n = 6） and sham surgery group （n = 6）. The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen （PCNA） staining was applied to study the effect of key miRNA overexpression on liver regeneration. Westenl blotting was used to validate the predicted target of the key miRNA. Results： Exosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in tile early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression ofmiR- 10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 （EphA4） has been predicted to be a target of miR-10a. The protein level of EpbA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle. Conclusion： Exosomal miR- 10a might accelerate liver regeneration through downregulation of EphA4.

Uly Alfi Nikmah,1,2,* Ariyani Noviantari,1,2,* Lisa Andriani Lienggonegoro1,2,*1Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Cibinong Science Center, Bogor, West Java, Indonesia*These authors contributed equally to this workCorrespondence: Lisa Andriani Lienggonegoro, Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Genomic Building, Cibinong Science Center, Jalan Raya Bogor Km. 46, Cibinong, Bogor, West Java, 16911, Indonesia, Email [email protected]View the original paper by Dr Jiang and colleagues

The microRNA (miRNA) miR-10 family has attracted attention because of its conservation and the position of the miR-10 genes within the Hox clusters of developmental regulators. In several species, miR-10 is coexpressed with a set of Hox genes and has been found to regulate the translation of Hox transcripts. In addition, members of the miR-10 family are de-regulated in several cancer forms. Aside from acting in translational repression, miR-10 was recently found to bind a group of transcripts containing a terminal oligo-pyrimidine (TOP) motif and to induce their translation, thereby adding a new function to the miRNA repertoire.