HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway

Chen, Yan-Qiang; Yang, Ting; Zhou, Bin; Yang, Minghan; Feng, Haijun; Wang, Yuliang

doi:10.1016/j.gene.2018.11.081

Cited by 23 publications

(16 citation statements)

References 41 publications

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“…Here, we revealed that Hoxa5 was direct target of miR-19a-3p and contribute to miR-19a-3p-induced BMSC osteogenic differentiation. Hoxa5 was served as tumor suppressor in a number of cancers including non-small cell lung cancer [28], osteosarcoma [29], gastric cancer [30] and gastric cancer [31]. Hoxa5 was also reported to alleviate inflammation and induce adipose tissue browning [32].…”

Section: Discussionmentioning

confidence: 99%

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

Chen¹,

Li²,

Zhi³

et al. 2020

Aging and disease

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The switch between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a key role in aging-induced osteoporosis. In this study, miR-19a-3p was obviously downregulated in BMSCs from aged humans and mice. Overexpressed miR-19a-3p evidently reduced aginginduced bone loss in mice and promoted osteogenic differentiation of BMSCs, while silenced miR-19a-3p manifestly increased aging-induced bone loss in mice and repressed osteogenic differentiation of BMSCs. Hoxa5 was significantly downregulated in the BMSCs from aged mice and contribute to miR-19a-3p-induced osteoblast differentiation as a direct target gene of miR-19a-3p. Furthermore, lncRNA Xist was found as a sponge of miR-19a-3p to repress BMSCs osteogenic differentiation. In conclusion, our study reveals the critical role of the lncRNA Xist/miR-19a-3p/Hoxa5 pathway in aging-induced osteogenic differentiation of BMSCs, indicating the potential therapeutic target for osteoporosis.

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Section: Discussionmentioning

confidence: 99%

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

Chen¹,

Li²,

Zhi³

et al. 2020

Aging and disease

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“…For example, accumulating evidence show that HOXA5 and HOXA10 are apoptosis-promoter genes. HOXA5 overexpression is associated with apoptosis in many cancers, including breast cancer [135,136], leukemia [137,138], osteosarcoma [139], lung [140], and cervical cancer [141]. In breast cancer cells, overexpression of HOXA5 promotes cell apoptosis by upregulating p53 expression [135] or activating caspase 2 and caspase 8 [136].…”

Section: Hox Genes In Cancer Progressionmentioning

confidence: 99%

The Role of HOX Transcription Factors in Cancer Predisposition and Progression

Huang

Wei

2019

Cancers

102

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Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer predisposition, and HOX genes might mediate the effect of many other cancer susceptibility factors by recognizing or executing altered genetic information. Remarkably, several lines of evidence highlight the interplays between HOX transcription factors and cancer risk loci discovered by genome-wide association studies, thereby gaining molecular and biological insight into cancer etiology. In addition, deregulated HOX gene expression impacts various aspects of cancer progression, including tumor angiogenesis, cell autophagy, proliferation, apoptosis, tumor cell migration, and metabolism. In this review, we will discuss the fundamental roles of HOX genes in cancer susceptibility and progression, highlighting multiple molecular mechanisms of HOX involved gene misregulation, as well as their potential implications in clinical practice.

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“…Besides, the gene dominance in expression level, that is, the aberrantly increased expression level of HOX genes in specific tissue types, the mechanism is also proposed to explain HOX genes relevant to cancer. The targets identified for HOX factors in human cancer are shown in Table 1 ( 4 – 7 , 13 – 20 , 25 – 30 , 32 – 35 , 38 – 49 , 55 – 62 , 65 – 70 , 74 – 76 , 80 – 83 , 86 – 91 , 116 – 121 , 127 – 130 , 133 – 149 ).…”

Section: Deregulation Of Hox Genes In Human Cancermentioning

confidence: 99%

“…HOXC8 in nasopharyngeal cancer is silent and its ectopic expression causes the inhibition of tumor growth ( 143 ). In vitro and in vivo , in addition, HOXA5 is often down-regulated in breast cancer and appears to mediate apoptosis through p53 or caspases 2 and 8 in normal cells, thus having a tumor-like effect inhibition ( 50 , 121 , 122 ). Downregulation of HOXC9 in infant neuroblastoma appears to lead to increased cancer cell survival and tumor growth ( 5 ).…”

Section: Deregulation Of Hox Genes In Human Cancermentioning

confidence: 99%

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

et al. 2021

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The homeobox (HOX) genes encoding an evolutionarily highly conserved family of homeodomain-containing transcriptional factors are essential for embryogenesis and tumorigenesis. HOX genes are involved in cell identity determination during early embryonic development and postnatal processes. The deregulation of HOX genes is closely associated with numerous human malignancies, highlighting the indispensable involvement in mortal cancer development. Since most HOX genes behave as oncogenes or tumor suppressors in human cancer, a better comprehension of their upstream regulators and downstream targets contributes to elucidating the function of HOX genes in cancer development. In addition, targeting HOX genes may imply therapeutic potential. Recently, novel therapies such as monoclonal antibodies targeting tyrosine receptor kinases, small molecular chemical inhibitors, and small interfering RNA strategies, are difficult to implement for targeting transcriptional factors on account of the dual function and pleiotropic nature of HOX genes-related molecular networks. This paper summarizes the current state of knowledge on the roles of HOX genes in human cancer and emphasizes the emerging importance of HOX genes as potential therapeutic targets to overcome the limitations of present cancer therapy.

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HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway

Cited by 23 publications

References 41 publications

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

The Role of HOX Transcription Factors in Cancer Predisposition and Progression

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

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