Chromosome 15 structural abnormalities: effect on IGF1R gene expression and function

Cannarella, Rossella; Mattina, Teresa; Condorelli, Rosita A.; Mongioì, Laura M.; Pandini, Giuseppe; Vignera, Sandro La; Calogero, Aldo E.

doi:10.1530/ec-17-0158

Cited by 25 publications

(34 citation statements)

References 69 publications

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“…In addition, qRT-PCR and western blotting confirmed the interrelationship between miR-23a and GAS5 at the transcriptional and protein levels. A previous study has shown that the lncRNA GAS5 can negatively regulate expression of miR-23a and that it can act as a miR-23a sponge [46] , which was in line with our conclusion. Furthermore, there is evidence that GAS5 expression is decreased in gastric cancer tissues and is negatively related to increased miR-23a expression [35] .…”

Section: Discussionsupporting

confidence: 93%

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

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Section: Discussionsupporting

confidence: 93%

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Wang

et al. 2018

Cell Physiol Biochem

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“…There were no differences in either the IGF-1R mRNA or protein levels. Both increased and decreased expression of the gene coding for IGF-1R (IGF1R) may play a role in the etiology of neurological disorders, as previous studies have described [Cannarella et al, 2017;Witsch et al, 2013]. We are the first to report on the levels of IGF-1R in human idiopathic autism.…”

Section: Discussionmentioning

confidence: 84%

Insulin‐Like Growth Factor and Insulin‐Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue

2020

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Autism spectrum disorder (ASD) is believed to stem from defects in the establishment and maintenance of functional neuronal networks due to synaptic/spine dysfunction. The potent effects of IGF‐1 on synaptic function, maintenance, and plasticity make it a potential target for treating ASD. This polypeptide hormone has proven to have beneficial effects in treating related developmental disorders like Rett syndrome, and its efficacy in ASD is currently being investigated in a pilot study. IGF‐1 binds to its receptor (IGF‐1R) in neurons and activates mitogen‐activated protein kinase and PI3K/Akt signaling to produce biological effects on spine function. The PI3K/Akt pathway is dysregulated in ASD, including idiopathic autism, and is thus believed to play a role in the disorder. Despite this, no study has explored the levels of IGF‐1 in the fusiform gyrus of idiopathic autism patients, an area known to be hypoactivated in ASD, and no study has examined IGF‐1R in any part of the brain. The present study explored whether IGF‐1 or IGF‐1R levels are altered in human idiopathic autism. RNA and protein were extracted from post‐mortem human fusiform gyrus tissue of normal controls (n = 20) and subjects with idiopathic autism (n = 15). qRT‐PCR for IGF‐1 and IGF‐1R were performed, along with total IGF‐1 ELISA and IGF‐1Rβ Western blots. The levels of both IGF‐1 and IGF‐1R mRNA and protein were equivalent between the two groups, suggesting that although IGF‐1 may be useful for ASD treatment, IGF‐1 and IGF‐1R are not implicated in the pathogenesis of idiopathic autism. Autism Res 2020, 13: 897‐907. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary IGF‐1 is being tested for the treatment of autism and related disorders. Despite promising results, it is unknown if IGF‐1 or its receptor are present in abnormal levels in patients with autism. This study showed that patients with autism have normal levels of IGF‐1 and its receptor in the brain, suggesting that although IGF‐1 is a promising treatment, disruption of IGF‐1 levels or signaling through its receptor does not seem to be a cause of autism.

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“…Interestingly, cryptorchidism and genital abnormalities have often been observed in patients with 15q structural abnormalities involving the IGF1R locus (Cannarella et al ., ). Such findings indicate a possible role of the IGF1/IGF1R signaling in testicular development, descent, and volume, and in genital differentiation.…”

Section: Evidence In Humansmentioning

confidence: 97%

“…After reviewing the literature, we found that cryptorchidism and other gonadal abnormalities often occur both in patients with 15q chromosome duplications and in those with ring chromosome 15 syndrome. Hence, we hypothesized that IGF1R , which maps on the 26.3 15q chromosomal band, may play a role in the onset of such features (Cannarella et al ., ). To further evaluate this topic, we focused our attention on the effects that the insulin‐like growth factor (IGF) system (mainly IGF1, IGF2, IGF1 receptor [IGF1R], insulin receptor substrates [IRS]) plays on testicular development and function.…”

Section: Introductionmentioning

confidence: 97%

Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

et al. 2017

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SUMMARYWe recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans. In animals, IGF1/IGF1R has been found to be involved in testicular development during embryogenesis, in Sertoli cell (SC) proliferation, and in germ cell (GS) proliferation and differentiation. Interestingly, IGF1R seems to mediate follicle-stimulating hormone (FSH) effects through the PI3K/AKT pathway. In humans, IGF1 directly increases testicular volume. The molecular pathways responsible for testicular differentiation and IGF1/IGF1R signaling are highly conserved among species; therefore, the IGF system may be involved in FSH signaling also in humans. We suggest a possible molecular pathway occurring in human SCs, which involves both IGF1 and FSH through the PI3K/AKT pathway. The acknowledgment of an IGF1 mediation of the FSH-induced effects may open new ways for a targeted therapy in idiopathic non-FSH-responder oligoasthenoteratozoospermia.

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Chromosome 15 structural abnormalities: effect on IGF1R gene expression and function

Cited by 25 publications

References 69 publications

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Insulin‐Like Growth Factor and Insulin‐Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue

Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

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