Modulation of HOXA9 after skeletal muscle denervation and reinnervation

Lü, Xiaomei; Liang, Bing-sheng; Li, Shuaijie; Chen, Zhi; Wenkai, Chang

doi:10.1152/ajpcell.00055.2020

Cited by 6 publications

(7 citation statements)

References 50 publications

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“…Overexpression of HOXA 9 significantly promoted the mRNA expression of BAD and BAX genes, reduced the expression of BCL 2 gene, and increased the apoptosis rate. Moreover, previous studies showed that HOXA 9 accelerated the apoptosis process of primary muscle satellite cells by affecting atrophic Signaling pathways [ 50 ] and negatively regulated downstream anti-apoptosis and autophagy-promoting genes (including BCL-XL , ULK 1, ATG 3 and ATG 12) of NF-κB to promote the apoptosis of skin squamous cell carcinoma (cSCC) cells and inhibit autophagy [ 51 ]. This meant HOXA 9 promoted cells apoptosis.…”

Section: Discussionmentioning

confidence: 99%

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes

He,

Feng,

et al. 2024

BMC Genomics

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Background Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. Result It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. Conclusion Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.

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Section: Discussionmentioning

confidence: 99%

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes

He,

Feng,

et al. 2024

BMC Genomics

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“…Several studies report that HOXA9 is involved in cell proliferation [ 38 – 40 ]. One study demonstrated that HOXA9 may promote denervated muscle atrophy by strongly upregulating MLL1 and WDR5 expression and inhibiting myogenic differentiation [ 23 ]. Furthermore, HOXA9 deletion improves satellite cell function and muscle regeneration in aged mice, whereas HOXA9 overexpression mimics age-associated defects in satellite cells from young mice, which can be rescued by inhibiting HOXA9-targeted developmental pathways.…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism involved in circRNAFUT10 and miR-365a-3p interactions needs to be further studied. In addition, Homeobox protein Hox-A9 (HOXA9) is related to denervated muscle atrophy [ 23 ], and inhibiting HOXA9 improved SkMSCs function and muscle regeneration in aged mice [ 24 ]. Similar to circRNA FUT10, bioinformatic analysis predicted the presence of binding sites for miR-365a-3p in the 3′-untranslated regions (UTRs) of HOXA9 mRNA.…”

Section: Introductionmentioning

confidence: 99%

CircRNA FUT10 regulates the regenerative potential of aged skeletal muscle stem cells by targeting HOXA9

Zhu

Lian

Chen

et al. 2021

Aging

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Skeletal muscle is capable of repairing itself after injury to maintain the stability of its own tissue, but this ability declines with aging. Circular RNAs (circRNAs) are involved in cell aging. However, there is little research into their role and underlying mechanisms, especially in skeletal muscle stem cells (SkMSCs). In this study, we assessed circRNA FUT10 expression in aged and adult SkMSCs. We observed that circRNA FUT10 was upregulated in aged SkMSCs compared with that in adult SkMSCs. Furthermore, we identified putative miR-365-3p binding sites on circRNA FUT10, suggesting that this circRNA sponges miR-365a-3p. We also found that HOXA9 is a downstream target of miR-365a-3p and confirmed that miR-365a-3p can bind to circRNA FUT10 and the 3′-untranslated region of HOXA9 mRNA. This finding indicated that miR-365a-3p might serve as a “bridge” between circRNA FUT10 and HOXA9. Finally, we found that the circRNA FUT10/miR365a-3p/HOXA9 axis is involved in SkMSC aging. Collectively, our results show that the circRNA FUT10/miR365a-3p/HOXA9 axis is a promising therapeutic target and are expected to facilitate the development of therapeutic strategies to improve the prognosis of degenerative muscle disease.

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“…HOXA9 expression is promoted by complexes composed of mixed lineage leukemia 1 (MLL1), a histone H3 lysine 4 (H3K4) methylransferase, and WD-40 repeat protein 5 (WDR5) [ 128 ]. Therefore, ruining the MLL1/WDR5 protein–protein interaction is a helpful means to indirectly target HOXA9.…”

Section: Wdr5-mll Inhibitorsmentioning

confidence: 99%

Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential

et al. 2022

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HOXA9 functioning as a transcription factor is one of the members of HOX gene family, which governs multiple cellular activities by facilitating cellular signal transduction. In addition to be a driver in AML which has been widely studied, the role of HOXA9 in solid tumor progression has also received increasing attention in recent years, where the aberrant expression of HOXA9 is closely associated with the prognosis of patient. This review details the signaling pathways, binding partners, post-transcriptional regulation of HOXA9, and possible inhibitors of HOXA9 in solid tumors, which provides a reference basis for further study on the role of HOXA9 in solid tumors.

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Modulation of HOXA9 after skeletal muscle denervation and reinnervation

Cited by 6 publications

References 50 publications

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes

CircRNA FUT10 regulates the regenerative potential of aged skeletal muscle stem cells by targeting HOXA9

Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential

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