MiRNAs as Players in Rhabdomyosarcoma Development

Gasparini, Patrizia; Ferrari, Andrea; Casanova, Michela; Limido, Francesca; Massimino, Maura; Sozzi, Gabriella; Fortunato, Orazio

doi:10.3390/ijms20225818

Cited by 12 publications

(15 citation statements)

References 63 publications

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“…During embryogenesis, the paired box transcription factors Pax3 and Pax7 regulate early MRFs. MRFs include transcription factors of the MyoD family, such as myogenin, Myf5, MyoD, MRF4 (also called Myf6), as well as the MEF2 family and the serum response factor (SRF) (15)(16)(17).…”

Section: Mirnas and Myogenesismentioning

confidence: 99%

Tiny Regulators of Massive Tissue: MicroRNAs in Skeletal Muscle Development, Myopathies, and Cancer Cachexia

2020

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Skeletal muscles are the largest tissues in our body and the physiological function of muscle is essential to every aspect of life. The regulation of development, homeostasis, and metabolism is critical for the proper functioning of skeletal muscle. Consequently, understanding the processes involved in the regulation of myogenesis is of great interest. Non-coding RNAs especially microRNAs (miRNAs) are important regulators of gene expression and function. MiRNAs are small (~22 nucleotides long) noncoding RNAs known to negatively regulate target gene expression post-transcriptionally and are abundantly expressed in skeletal muscle. Gain- and loss-of function studies have revealed important roles of this class of small molecules in muscle biology and disease. In this review, we summarize the latest research that explores the role of miRNAs in skeletal muscle development, gene expression, and function as well as in muscle disorders like sarcopenia and Duchenne muscular dystrophy (DMD). Continuing with the theme of the current review series, we also briefly discuss the role of miRNAs in cancer cachexia.

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Section: Mirnas and Myogenesismentioning

confidence: 99%

Tiny Regulators of Massive Tissue: MicroRNAs in Skeletal Muscle Development, Myopathies, and Cancer Cachexia

2020

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“…Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, listing among the top 20 most diagnosed cancers in the world [ 1 , 2 ]. RMS is a typical embryonal tumor in childhood, characterized by skeletal muscle differentiation (WHO STS 2013) [ 3 ]. Overall, the incidence of RMS is 4.3 million/year worldwide; two-thirds of all cases are diagnosed before seven years old.…”

Section: Introductionmentioning

confidence: 99%

“…Overall, the incidence of RMS is 4.3 million/year worldwide; two-thirds of all cases are diagnosed before seven years old. Although it occurs mainly in children's age group (0–10 years old), it also has a high incidence in puberty and youth (15–30 years old), but it is extremely rare in adults [ 3 ]. Histologically, RMS can be classified into two major histotypes: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although it occurs mainly in children's age group (0–10 years old), it also has a high incidence in puberty and youth (15–30 years old), but it is extremely rare in adults [ 3 ]. Histologically, RMS can be classified into two major histotypes: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) [ 3 ]. ERMS accounts for about 80% of all cases and usually affects children aged 0–4 years, occurring in the neck, head, and reproductive urinary tract; ARMS, a highly malignant tumor that mainly occurs in teenagers, accounts for about 20% of RMS cases [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Adiponectin Deficiency Suppresses Rhabdomyosarcoma Associated with Gut Microbiota Regulation

Jiao

Wang

Huang

et al. 2021

BioMed Research International

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The gut microbiota is very important in the initiation, progression, and dissemination of cancer, and the regulation of microbiota has been employed as a novel strategy to enhance the effect of immunotherapy. Adiponectin (APN), an adipocyte-derived hormone, plays a vital role in regulating the immune response of innate immune cells. The deficiency of APN inhibits rhabdomyosarcoma growth. However, whether this function is associated with regulating gut microbiota remains unknown. To investigate, we performed 16S ribosomal RNA (rRNA) gene sequencing on the fecal microbiome of APN gene knockout mice to determine whether APN deletion affects the gut microbiota. We found APN deficiency alters gut microbial functions involved in metabolism, genetic information processing, and cellular processes. In addition, a decreased abundance of Bacteroides and an increased abundance of Prevotella and Helicobacter were observed in rhabdomyosarcoma-bearing APN knockout mice; these bacteria were associated with the inhibition of rhabdomyosarcoma growth. These findings suggest that gut microbiota may be a potential target of APN deficiency against rhabdomyosarcoma.

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“…Interestingly, in RMS myomiRs, that result significantly downregulated, act in concert with other non-muscle miRNAs (miR-29, miR-26a, and miR-183) impairing myogenesis and proliferation. MyomiRs in RMS interact directly with PAX3 and PAX7 genes as well as with cell cycle regulator Cyclin D2 and cMET oncogene ( Rota et al, 2011 ; Li et al, 2012 ; Gasparini et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma

et al. 2020

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Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

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MiRNAs as Players in Rhabdomyosarcoma Development

Cited by 12 publications

References 63 publications

Tiny Regulators of Massive Tissue: MicroRNAs in Skeletal Muscle Development, Myopathies, and Cancer Cachexia

Tiny Regulators of Massive Tissue: MicroRNAs in Skeletal Muscle Development, Myopathies, and Cancer Cachexia

Adiponectin Deficiency Suppresses Rhabdomyosarcoma Associated with Gut Microbiota Regulation

Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma

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