KMT5A Knockdown Suppresses Osteosarcoma Cell Proliferation and Metastasis Through Ꞵ-Catenin Signalling

Zhang, Jin; An, Jiangdong; Wang, Zhaoheng; Wang, Keping; Liang, Wei; Liu, Xiangyu; Zhou, Hai-Yu; Zhang, Haihong; Wang, Shuankev

doi:10.25011/cim.v45i3.38933

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…2B). Furthermore, we compared the expression of three genes that have been demonstrated in other studies to be associated with lung metastasis in OS [13][14][15]. The results indicate high expression of these genes in MLN and PT (all p < 0.05, Wilcoxon test), suggesting that these genes may also be involved in the LN metastasis (Fig.…”

Section: Transcriptional Characteristics Of Osteoblast Cells During T...mentioning

confidence: 77%

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma

Liu,

He,

Tang

et al. 2024

BMC Med

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Background Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. Methods Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. Results From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. Conclusions Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

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Section: Transcriptional Characteristics Of Osteoblast Cells During T...mentioning

confidence: 77%

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma

Liu,

He,

Tang

et al. 2024

BMC Med

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“…In addition, the ectopic expression of miR-335 or the deletion of its target gene KMT5A can enhance the sensitivity of paclitaxel-resistant breast cancer cells to paclitaxel [22]. Similarly, An et al [23] found that KMT5A promotes the expression of downstream molecules by activating the β-catenin signaling pathway, thereby increasing the proliferation and metastasis of osteosarcoma cells. In our previous studies, we discovered that LINC00473 down-regulates miR-502-3p and up-regulates KMT5A through the ceRNA mechanism, thereby regulating the cell cycle through the LINC00473/miR-502-3p/KMT5A signaling axis, and affecting the proliferation and invasion of pituitary adenomas [15].…”

Section: Discussionmentioning

confidence: 99%

Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/β-Catenin Signaling Pathway

Li,

Song,

Chen

et al. 2024

Neuroendocrinology

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Introduction: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine Methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. Methods: Immunohistochemistry, qRT-PCR and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, Flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. Results: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation and FCM assays. Additionally, WB analysis identified the Wnt/β-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. Conclusion: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/β-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

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Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia

Novakov

Novakova

Churnosova

et al. 2023

Life

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This study was conducted to examine the associations between genome-wide association studies (GWAS)-important single nucleotide polymorphisms (SNPs) and knee osteoarthritis (KOA) among Europeans of Russia. The present replicative study (“patient-control” design has been used) was carried out on 1000 DNA samples from KOA (n = 500) and KOA-free (n = 500) participants. Ten GWAS-important for KOA SNPs of eight candidate genes (LYPLAL1, GNL3, GLT8D1, SBNO1, WWP2, NFAT5, TGFA, GDF5) were studied. To assess the link between SNPs and KOA susceptibility, logistic regression (to establish independent SNP effects) and MB-MDR (to identify SNP–SNP interactions) were used. As a result of this genetic analysis, the associations of individual SNPs with KOA have not been proven. Eight loci out of ten tested SNPs interacted with each other (within twelve genetic models) and determined susceptibility to KOA. The greatest contribution to the disease development were made by three polymorphisms/genes such as rs6976 (C>T) GLT8D1, rs56116847 (G>A) SBNO1, rs6499244 (T>A) NFAT5 (each was included in 2/3 [8 out 12] KOA-responsible genetic interaction models). A two-locus epistatic interaction of rs56116847 (G >A) SBNO1 × rs6499244 (T>A) NFAT5 determined the maximum percentage (0.86%) of KOA entropy. KOA-associated SNPs are regulatory polymorphisms that affect the expression/splicing level, epigenetic modification of 72 genes in KOA-pathogenetically significant organs such as skeletal muscles, tibial arteries/nerves, thyroid, adipose tissue, etc. These putative KOA-effector genes are mainly involved in the organization/activity of the exoribonuclease complex and antigen processing/presentation pathways. In conclusion, KOA susceptibility among Europeans of Russia is mediated by intergenic interactions (but not the main effects) of GWAS-important SNPs.

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KMT5A Knockdown Suppresses Osteosarcoma Cell Proliferation and Metastasis Through Ꞵ-Catenin Signalling

Cited by 3 publications

References 31 publications

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma

Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma

Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/β-Catenin Signaling Pathway

Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia

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