HTR2B and SLC5A3 Are Specific Markers in Age-Related Osteoarthritis and Involved in Apoptosis and Inflammation of Osteoarthritis Synovial Cells

Lu, Xin; Fan, Yu; Li, Mingxia; Chang, Xiao; Qian, Jun

doi:10.3389/fmolb.2021.691602

Cited by 8 publications

(5 citation statements)

References 35 publications

(37 reference statements)

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“…In vivo, it participates in oxidative stress and positive regulation of reactive oxygen species (ROS) biosynthetic process, inflammation, inositol transport, regulation of osmotic pressure, ion channels, cell proliferation and apoptosis, vasoconstriction, and so on. Diseases involved in the study include neuropsychiatric diseases (schizophrenia and Parkinson’s disease) [ 31 , 32 ], diseases of the musculoskeletal system (osteoarthritis, myositis, and lumbar disc herniation) [ 33 – 35 ], endocrine diseases (polycystic ovary syndrome, diabetes, and obesity) [ 36 , 37 ], acute renal injury [ 38 ], non-small cell lung cancer [ 39 ], and so on. In the field of blood system diseases, there are studies primarily on acute myeloid leukemia.…”

Section: Discussionmentioning

confidence: 99%

METTL16 participates in haemoglobin H disease through m6A modification

Liao,

Zhang,

Yang

et al. 2024

PLoS ONE

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Background Haemoglobin H (HbH) disease is caused by a disorder of α-globin synthesis, and it results in a wide range of clinical symptoms. M6A methylation modification may be one of the mechanisms of heterogeneity. Therefore, this article explored the role of methyltransferase like 16 (METTL16) in HbH disease. Method The results of epigenetic transcriptome microarray were analysed and verified through bioinformatic methods and qRT-PCR, respectively. The overexpression or knock down of METTL16 in K562 cells was examined to determine its role in reactive oxygen species (ROS), cell cycle processes or iron overload. YTH domain family protein 3 (YTHDF3) was knocked down in K562 cells and K562 cells overexpressing METTL16 via siRNA to investigate its function. In addition, haemoglobin expression was detected through benzidine staining. qRT-PCR, WB, methylated RNA Immunoprecipitation (MeRIP) and (RNA Immunoprecipitation) RIP experiments were conducted to explore the mechanism of intermolecular interaction. Results METTL16, YTHDF3 and solute carrier family 5 member 3 (SLC5A3) mRNA and the methylation level of SLC5A3 mRNA were downregulated in HbH patients. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA expression was negatively correlated with HGB content among patients with HbH-CS disease. Overexpression of METTL16 increased ROS and intracellular iron contents in K562 cells, changed the K562 cell cycle, reduced hemin-induced haemoglobin synthesis, increased the expressions of SLC5A3 and HBG and increased SLC5A3 mRNA methylation levels. Knockdown of METTL16 reduced ROS and intracellular iron contents in K562 cells. Hemin treatment of K562 cells for more than 14 days reduced the protein expressions of METTL16 and SLC5A3 and SLC5A3 mRNA methylation levels. Knockdown of YTHDF3 rescued the intracellular iron content changes induced by the overexpression of METTL16. The RIP experiment revealed that SLC5A3 mRNA can be enriched by METTL16 antibody. Conclusion METTL16 may affect the expression of SLC5A3 by changing its m6A modification level and regulating ROS synthesis, intracellular iron and cycle of red blood cells. Moreover, METTL16 possibly affects the expression of haemoglobin through IGF2BP3, which regulates the clinical phenotype of HbH disease.

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Section: Discussionmentioning

confidence: 99%

METTL16 participates in haemoglobin H disease through m6A modification

Liao,

Zhang,

Yang

et al. 2024

PLoS ONE

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“…qRT-PCR and Western blotting protocols were reported early 17 . mRNA primers for SLC5A3 and SLC5A11 were described early 24 , 25 . Figure S1 included the uncropped blotting images.…”

Section: Methodsmentioning

confidence: 99%

SLC5A3 is important for cervical cancer cell growth

Li¹,

Shen²,

Cheng³

et al. 2023

Int. J. Biol. Sci.

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Novel molecular targets for cervical cancer must be identified. This study examined the role of SLC5A3, a myo-inositol transporter, in the pathogenesis of cervical cancer. Through boinformatics analysis, we showed that the SLC5A3 mRNA levels were upregulated in cervical cancer tissues. The upregulated SLC5A3 mRNA levels were negatively correlated with survival and progression-free interval. Genes co-expressed with SLC5A3 were enriched in multiple signaling cascades involved in cancer progression. In primary/established cervical cancer cells, SLC5A3 shRNA/knockout (KO) exerted growth-inhibitory effects and promoted cell death/apoptosis. Furthermore, SLC5A3 knockdown or KO downregulated myo-inositol levels, induced oxidative injury, and decreased Akt-mTOR activation in cervical cancer cells. In contrast, supplementation of myo-inositol or n-acetyl-L-cysteine or transduction of a constitutively active Akt1 construct mitigated SLC5A3 KO-induced cytotoxicity in cervical cancer cells. Lentiviral SLC5A3 overexpression construct transduction upregulated the cellular myo-inositol level and promoted Akt-mTOR activation, enhancing cervical cancer cell proliferation and migration. The binding of TonEBP to the SLC5A3 promoter was upregulated in cervical cancer. In vivo studies showed that intratumoral injection of SLC5A3 shRNA-expressing virus arrested cervical cancer xenograft growth in mice. SLC5A3 KO also inhibited pCCa-1 cervical cancer xenograft growth. The SLC5A3-depleted xenograft tissues exhibited myo-inositol downregulation, Akt-mTOR inactivation, and oxidative injury. Transduction of sh-TonEBP AAV construct downregulated SLC5A3 expression and inhibited pCCa-1 cervical cancer xenograft growth. Together, overexpressed SLC5A3 promotes growth of cervical cancer cells, representing as a novel therapeutic oncotarget for the devastating disease.

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“…Two different SLC5A3 shRNAs, shSLC5A3-S1 and shSLC5A3-S2 (containing non-overlapping sequences [ 17 ]), or the SLC5A3-expressing cDNA sequence [ 8 ], were individually sub-cloned into a GV248 construct. The shRNA construct or the overexpression construct was then transfected to HEK-293T cells along with the described lentivirus package constructs [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Data quantification was described previously [ 12 ]. Primers for SLC5A3 , ISYNA1 , and GAPDH were described previously [ 17 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

The sodium/myo-inositol co-transporter SLC5A3 promotes non-small cell lung cancer cell growth

Cui

et al. 2022

Cell Death Dis

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Identification of novel molecular signaling targets for non-small cell lung cancer (NSCLC) is important. The present study examined expression, functions and possible underlying mechanisms of the sodium/myo-inositol co-transporter SLC5A3 in NSCLC. The Cancer Genome Atlas (TCGA) database and local NSCLC tissue results demonstrated that SLC5A3 expression in NSCLC tissues (including patient-derived primary NSCLC cells) was significantly higher than that in normal lung tissues and lung epithelial cells. In primary NSCLC cells and immortalized lines, SLC5A3 depletion, using small hairpin RNA (shRNA) and CRSIRP/Cas9 methods, robustly impeded cell proliferation and migration, simultaneously provoking cell cycle arrest and apoptosis. Conversely, ectopic overexpression of SLC5A3 further enhanced proliferation and migration in primary NSCLC cells. The intracellular myo-inositol contents and Akt-mTOR activation were largely inhibited by SLC5A3 silencing or knockout (KO), but were augmented following SLC5A3 overexpression in primary NSCLC cells. Significantly, SLC5A3 KO-induced anti-NSCLC cell activity was largely ameliorated by exogenously adding myo-inositol or by a constitutively-active Akt construct. By employing the patient-derived xenograft (PDX) model, we found that the growth of subcutaneous NSCLC xenografts in nude mice was largely inhibited by intratumoral injection SLC5A3 shRNA adeno-associated virus (AAV). SLC5A3 silencing, myo-inositol depletion, Akt-mTOR inactivation and apoptosis induction were detected in SLC5A3 shRNA virus-injected NSCLC xenograft tissues. Together, elevated SLC5A3 promotes NSCLC cell growth possibly by maintaining myo-inositol contents and promoting Akt-mTOR activation.

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HTR2B and SLC5A3 Are Specific Markers in Age-Related Osteoarthritis and Involved in Apoptosis and Inflammation of Osteoarthritis Synovial Cells

Cited by 8 publications

References 35 publications

METTL16 participates in haemoglobin H disease through m6A modification

METTL16 participates in haemoglobin H disease through m6A modification

SLC5A3 is important for cervical cancer cell growth

The sodium/myo-inositol co-transporter SLC5A3 promotes non-small cell lung cancer cell growth

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