The non‐human primate kidney transcriptome in fetal development

Spradling-Reeves, Kimberly D.; Glenn, Jeremy P.; Lange, Kenneth; Kuhn, Natalia; Coalson, Jacqueline J.; Nijland, Mark J.; Li, Cun; Nathanielsz, Peter W.; Cox, Laura A.

doi:10.1111/jmp.12340

Cited by 3 publications

(2 citation statements)

References 25 publications

(49 reference statements)

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“…In addition, three GEO datasets related to embryonic development were also used in this study, including GSE65162 [ 36 ], GSE20954 [ 37 ], and GSE128419 [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development

Lv,

Wei,

Zhang

et al. 2024

Cell Mol Biol Lett

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Background IGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended. Methods The mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays. Results We observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses. Conclusions Our present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer. Graphical Abstract

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“…In addition, three GEO datasets related to embryonic development were also used in this study, including GSE65162 [ 36 ], GSE20954 [ 37 ], and GSE128419 [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development

Lv,

Wei,

Zhang

et al. 2024

Cell Mol Biol Lett

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“…Total RNA was isolated with quality checks, and complementary RNA (cRNA) was synthesized and biotinylated as described in 35 using HumanHT‐12 v3 Expression BeadChips (Illumina, Inc.).…”

Section: Methodsmentioning

confidence: 99%

Postnatal persistence of nonhuman primate sex‐dependent renal structural and molecular changes programmed by intrauterine growth restriction

Bishop

Spradling-Reeves

Shade

et al. 2022

J of Medical Primatology

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Background Poor nutrition during fetal development programs postnatal kidney function. Understanding postnatal consequences in nonhuman primates (NHP) is important for translation to our understanding the impact on human kidney function and disease risk. We hypothesized that intrauterine growth restriction (IUGR) in NHP persists postnatally, with potential molecular mechanisms revealed by Western‐type diet challenge. Methods IUGR juvenile baboons were fed a 7‐week Western diet, with kidney biopsies, blood, and urine collected before and after challenge. Transcriptomics and metabolomics were used to analyze biosamples. Results Pre‐challenge IUGR kidney transcriptome and urine metabolome differed from controls. Post‐challenge, sex and diet‐specific responses in urine metabolite and renal signaling pathways were observed. Dysregulated mTOR signaling persisted postnatally in female pre‐challenge. Post‐challenge IUGR male response showed uncoordinated signaling suggesting proximal tubule injury. Conclusion Fetal undernutrition impacts juvenile offspring kidneys at the molecular level suggesting early‐onset blood pressure dysregulation.

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