Growth hormone receptor promotes osteosarcoma cell growth and metastases

Cheng, Mo; Huang, Wending; Cai, Weiluo; Fang, Meng; Chen, Yong; Wang, Chunmeng; Yan, Wangjun

doi:10.1002/2211-5463.12761

Cited by 9 publications

(9 citation statements)

References 30 publications

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“…[46][47][48] IGF-1 is produced in the liver, stimulated by GH, and plays a main role in tissue growth and development. [49][50][51][52] Higher circulating levels of IGF-1 have a profound impact on cell proliferation, differentiation, promotion of cellular longevity, and inhibition of apoptosis. 53,54 Consequently, overexpression of IGF-1/IGF-1R has been implicated in tumor formation, angiogenesis, and metastasis in various human cancer types, including OS.…”

Section: Discussionmentioning

confidence: 99%

“…55 Thus, increasing GHR expression level will lead to higher circulating levels of IGF-1 and may eventually result in tumorigenesis. [47][48][49]53,55 Dysregulation of LEPROT is associated with various bone inflammation diseases in humans through the key inflammatory cytokines such as tumor necrosis factor alpha (TNF a) and interleukin 6 (IL-6). Several studies have highlighted that bone inflammation is a frequent precursor to initiation and progression of OS.…”

Section: Discussionmentioning

confidence: 99%

“…55 Thus, increasing GHR expression level will lead to higher circulating levels of IGF-1 and may eventually result in tumorigenesis. 47–49,53,55…”

Section: Discussionmentioning

confidence: 99%

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Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Rothzerg

et al. 2020

Exp Biol Med (Maywood)

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Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR <0.05) 26 differentially expressed transcript variants of leptin receptor overlapping transcript ( LEPROT) gene. Some of the transcripts were overexpressed in normal cells, whereas others were overexpressed in tumor cells. The function of LEPROT is not completely understood. Herein, we highlight a possible association between OS and aberrant alternative splicing events and its interaction with the expression of LEPROT. We also discuss the role of LEPROT in regulating growth hormone and its receptor, and the relationship with initiation and progression of OS. This research study may help to understand the association of alternative splicing mechanism in OS and in tumorigenesis more generally. Further, LEPROT gene can also be considered as a potential biomarker of osteosarcoma. Impact statement Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal—tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of LEPROT gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Rothzerg

et al. 2020

Exp Biol Med (Maywood)

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“…The MAPK pathway and the PI3K/AKT pathway are important for pituitary tumorigenesis (34) and are activated also by the GH and IGF signaling. Osteosarcoma is the most prevalent bone malignancy in children and adolescents and is a main cause of cancer-related deaths (35). Interestingly, a recent study reported the overexpression of GHR in osteosarcoma samples and that GHR gene knockdown reduced proliferation, invasion and migration while increasing apoptosis (35).…”

Section: Mirnas and Lncrnas Regulating The Gh/igf1 Axis And Igf System In Cancer: Focus On Pituitary Adenoma Osteosarcoma And Colorectal mentioning

confidence: 99%

GH and IGF System: The Regulatory Role of miRNAs and lncRNAs in Cancer

et al. 2021

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Growth hormone (GH) and the insulin-like growth factor (IGF) system are involved in many biological processes and have growth-promoting actions regulating cell proliferation, differentiation, apoptosis and angiogenesis. A recent chapter in epigenetics is represented by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) which regulate gene expression. Dysregulated miRNAs and lncRNAs have been associated with several diseases including cancer. Herein we report the most recent findings concerning miRNAs and lncRNAs regulating GH and the IGF system in the context of pituitary adenomas, osteosarcoma and colorectal cancer, shedding light on new possible therapeutic targets. Pituitary adenomas are increasingly common intracranial tumors and somatotroph adenomas determine supra-physiological GH secretion and cause acromegaly. Osteosarcoma is the most frequent bone tumor in children and adolescents and was reported in adults who were treated with GH in childhood. Colorectal cancer is the third cancer in the world and has a higher prevalence in acromegalic patients.

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“…Adult height has been used as a biomarker of GH and IGF‐1 action, which is an independent risk for malignancy . Recently, it was also reported that GHR modulates osteosarcoma cell proliferation and metastasis through the phosphoinositide 3‐kinase/AKT signaling pathway . Previous studies have reported that individuals taller than 175 cm have a 20% higher risk for prostate cancer, a 22% higher risk for breast cancer and a 20–60% higher risk for colorectal cancer compared with control subjects shorter than 160 cm .…”

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confidence: 99%

Growth hormone receptor promotes breast cancer progression via the BRAF/MEK/ERK signaling pathway

Zhu

et al. 2020

FEBS Open Bio

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Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably inhibited GHR in breast cancer cell lines, which were observed to reduce cell proliferation, tumor growth and induction of apoptosis, and arrest the cell‐cycle arrest at the G1–S phase transition. In addition, GHR silencing suppressed the protein levels of B‐Raf proto‐oncogene, serine/threonine kinase (BRAF), Mitogen‐activated protein kinase kinase (MEK) and Extracellular regulated protein kinases (ERK). These findings suggest that GHR may mediate breast cell progression and apoptosis through control of the cell cycle via the BRAF/MEK/ERK signaling pathway.

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Growth hormone receptor promotes osteosarcoma cell growth and metastases

Cited by 9 publications

References 30 publications

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

GH and IGF System: The Regulatory Role of miRNAs and lncRNAs in Cancer

Growth hormone receptor promotes breast cancer progression via the BRAF/MEK/ERK signaling pathway

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