ABSTRACT
Senescent pre-osteoblasts have a reduced ability to differentiate, which leads to a reduction in bone formation. It is critical to identify the keys that regulate the differentiation fate of senescent pre-osteoblasts. LINC01013 has an essential role in cell stemness, differentiation, and senescence regulation. This study aims to examine the role and mechanism of LINC01013 in regulating osteogenic differentiation in senescent human embryonic osteoblast cell line (hFOB1.19) cells induced by hydrogen peroxide (H2O2). The results show that LINC01013 decreased alkaline phosphatase activity, mineralization of hFOB1.19 cells in vitro, and the expression of collagen II, osteocalcin, and bone sialoprotein. LINC01013 knockdown enhances the osteogenesis of hFOB1.19 cells and rescues osteogenic differentiation impaired by H2O2. METTL3 negatively regulates LINC01013 expression, enhancing hFOB1.19 cells' osteogenesis in vitro and in vivo. METTL3 overexpression can enhance hFOB1.19 cells' osteogenic differentiation impaired by H2O2. YTHDF2 promotes LINC01013 decay, facilitating osteogenic differentiation. YTHDF2 overexpression rescues hFOB1.19 cells osteogenic differentiation impaired by H2O2. Taken together, METTL3 upregulates osteogenic differentiation by inhibiting LINC01013, and YTHDF2 accelerates LINC01013 degradation, reducing its inhibitory effect. This study highlights LINC01013 as a key regulator in the fate switching process of senescent hFOB1.19 cells, impacting osteogenic differentiation.
Subject(s)
Cell Differentiation , Cellular Senescence , Hydrogen Peroxide , Methyltransferases , Osteoblasts , Osteogenesis , RNA, Long Noncoding , Animals , Humans , Mice , Cell Differentiation/drug effects , Cell Line , Cellular Senescence/drug effects , Hydrogen Peroxide/pharmacology , Methyltransferases/genetics , Methyltransferases/metabolism , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Osteogenesis/drug effects , Osteogenesis/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored current literature on lncRNA expression in ALL to identify lncRNAs consistently reported as differentially expressed (DE) either in ALL versus controls or between ALL subtypes. By comparing articles that provided global expression data for DE lncRNAs in the ETV6::RUNX1-positive ALL subtype, we identified four DE lncRNAs in three independent studies (two versus other subtypes and one versus controls), showing concordant expression of LINC01013, CRNDE and lnc-KLF7-1. Additionally, LINC01503 was consistently downregulated on ALL versus controls. Within RT-qPCR studies, twelve lncRNA were DE in more than one source. Thus, several lncRNAs were supported as DE in ALL by multiple sources, highlighting their potential role as candidate biomarkers or therapeutic targets. Finally, as lncRNA annotation is rapidly expanding, standardization of reporting and nomenclature is urgently needed to improve data verifiability and compilation.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Biomarkers/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Gene Expression Profiling , Kruppel-Like Transcription Factors/geneticsABSTRACT
Cancer stem cells (CSCs) are major contributors to tumor initiation, recurrence, and metastasis of hepatocellular carcinoma (HCC). Some long non-coding RNAs have been reported as modulators of stem-like properties in cancer cells. However, the role of LINC01013 in liver CSCs has not yet been clarified. In this study, we aimed to elucidate the expression pattern and functions of LINC01013 in HCC. HCC tissues and normal controls were collected, and the expression pattern of LINC01013 and miR-6795-5p was identified by quick real-time polymerase chain reaction. Cell counting kit-8 assay, colony formation, and spheroid formation were performed to measure cell viability, proliferation, and self-renewal of HCC cell lines. The expression of stem markers was detected by western blot analysis. The effect of LINC01013 on viability, proliferation, and stem-like properties was detected through gain-of-function and loss-of-function experiments. The direct interaction among LINC01013, miR-6795-5p, and FMNL3 was testified by dual-luciferase reporter gene assay. Tumor-bearing mice were constructed to ascertain the functions of LINC01013 in vivo. HCC tissues showed increased LINC01013 and FMNL3 expression, while it showed a decreased miR-6795-5p expression as compared to the relative controls. Moreover, the high level of LINC01013 was closely related to the poor prognosis of HCC patients. LINC01013 directly binds to miR-6795-5p and subsequently relieves FMNL3. Silencing LINC01013, FMNL3, or overexpression of miR-6795-5p could suppress spheroid and colony formation, proliferation, as well as expression of stemness markers in HepG2 and SNU-182 cells. LINC01013 knockdown suppressed growth and stem-like traits of HCC cells in vivo by reducing FMNL3 expression. LINC01013/miR-6795-5p/FMNL3 axis may be a novel therapeutic target for HCC.