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MiR-335-5P contributes to human osteoarthritis by targeting HBP1

ABSTRACT: MicroRNA (miR)-335-5P has the ability to regulate chondrogenic differentiation and promote chondrogenesis in mouse mesenchymal stem cells. It is also abnormally elevated in human osteoarthritic chondrocytes. However, the biological function of miR-335-5P in osteoarthritis (OA) is not well understood. The present study investigated the mechanism of miR-335-5P in the pathogenesis of OA. To investigate the effect of miR-335-5P on the pathogenesis of OA in vitro, a miR-335-5P mimic and inhibitor were transfected into chondrocytes. Cell Counting kit-8 assay and flow cytometry were used to observe the effects of miR-335-5P on chondrocyte apoptosis and the expression of cartilage-specific genes, such as aggrecan, collagen II, matrix metalloproteinase 13 and collagen X, were detected by reverse transcription-quantitative PCR and western blot analysis. Moreover, the current study assessed whether HMG-box transcription factor 1 (HBP1) is a novel target of miR-335-5P with dual luciferase reporter assays. Finally, a rescue experiment was used to prove the regulation between miR-335-5P and HBP1. The results revealed that HBP1 was a novel target of miR-335-5P, and that miR-335-5P mediated the apoptosis of chondrocytes and changes in cartilage-specific genes via targeting HBP1. Overall, the present study revealed that miR-335-5P mediated the development of OA by targeting the HBP1 gene and promoting chondrocyte apoptosis. These data suggested that miR-335-5P may be used to develop novel early-stage diagnostic and therapeutic strategies for OA.

SUBMITTER: Lu X

PROVIDER: S-EPMC7739851 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Project description:This study demonstrated that miR‐335‐5p expression was reduced in HNSCC. miR‐335‐5p expression could inhibit HNSCC cell growth, metastasis, and promote cell apoptosis while it could suppress tumor growth in vivo. We identified MAP3K2 as a novel target of miR‐335‐5p and MAP3K2 overexpression partially rescued the inhibitory role of miR‐335‐5p. Hence, miR‐335‐5p might constitute a potential therapeutic target for HNSCC patients. Mounting evidence has indicated that aberrantly expressed microRNAs (miRNAs) play key roles in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that miR‐335‐5p can serve as a tumor suppressor or an oncogene in cancer. However, the clinical importance and biological effects of miR‐335‐5p in HNSCC have not been determined. Here, we investigated the expression pattern, functional role, and mechanisms of miR‐335‐5p in HNSCC. We showed a decreased expression of miR‐335‐5p in HNSCC samples from the TCGA and GEO databases. Consistently, we detected a downregulation of miR‐335‐5p in HNSCC cell lines and patient tissues. The expression of miR‐335‐5p was inversely correlated with advanced clinical TNM stage and lymph node metastasis in HNSCC patients. miR‐335‐5p overexpression inhibited HNSCC cell proliferation and induced apoptosis, while miR‐335‐5p inhibition had the opposite effects. miR‐335‐5p overexpression suppressed tumor growth in mice. Bioinformatic analyses and functional assays identified MAP3K2 as a target of miR‐335‐5p, and we showed that miR‐335‐5p downregulated mitogen‐activated protein kinase kinase kinase 2 (MAP3K2) expression in HNSCC cells. We found an inverse association between MAP3K2 and miR‐335‐5p expression in 38 pairs of HNSCC tissues. Furthermore, the effect of miR‐335‐5p overexpression on growth and metastasis as well as cell apoptosis in HNSCC cells could be partially rescued by MAP3K2 expression. Collectively, our data show that miR‐335‐5p inhibits the development of HNSCC by regulating MAP3K2 expression. Thus, these findings offer novel insights into a potential therapeutic strategy for HNSCC patients.

Project description:BackgroundKawasaki disease (KD) is an autoimmune disease with systemic vasculitis as the main pathological change, and is most common in children under 5. The role of long non-coding RNAs (lncRNAs) in human diseases has been highlighted. LncRNA Slco4a1 was reported to promote cell growth and act as an oncogenic regulator in cancer. However, the role of lncRNA Slco4a1 in KD remains unclear. This study aimed to investigate the role and mechanism of lncRNA Slco4a1 in KD.MethodsEnzyme linked immunosorbent assay (ELISA), qRT-PCR, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were conducted to explore the function of lncRNA Slco4a1. The interaction between POU5F1 and miR-335-5p was analyzed by the RIP assay and dual luciferase assay.ResultsLncRNA Slco4a1 was significantly upregulated in the serum of KD patients compared with healthy controls. LncRNA Slco4a1 was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated with KD serum. LncRNA Slco4a1 overexpression could promote the expression of inflammatory factors and apoptosis in HUVECs. The number of inflammatory cells and the infiltration area of the coronary artery in KD rats were decreased after lncRNA Slco4a1 silencing. Furthermore, lncRNA Slco4a1 is a sponge of miR-335-5p and negatively regulated the expression of miR-335-5p. POU5F1 was the downstream target of miR-335-5p, and miR-335-5p overexpression could upregulate the expression of POU5F1. Additionally, miR-335-5p overexpression could inhibit the expression of inflammatory factors and apoptosis in HUVECs. We further investigated the effect of lncRNA Slco4a1 on the mitogen-activated protein kinase (MAPK) signaling pathway, and the results showed that lncRNA Slco4a1 could promote the activation of the MAPK signaling pathway.ConclusionsTogether, these results indicated that lncRNA Slco4a1 could regulate the progression of HUVECs in KD by targeting the miR-335-5p/POU5F1 axis, providing new insights for KD treatment.

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MiR-335-5P contributes to human osteoarthritis by targeting HBP1

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