lncRNA Chronos is an aging-induced inhibitor of muscle hypertrophy

Neppl, Ronald L.; Wu, Chia Ling; Walsh, Kenneth

doi:10.1083/jcb.201612100

Cited by 44 publications

(42 citation statements)

References 39 publications

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“…The present data suggest that serum OIS1 may serve as an effective diagnostic biomarker in patients with HPV-positive cervical squamous cell carcinoma. Expression of lncRNAs is regulated by various factors, including aging (17), tobacco consumption (18) and alcohol abuse (19). In the present study, serum levels of OIS1 exhibited no significant association with patient age, smoking or alcohol consumption.…”

Section: Discussioncontrasting

confidence: 62%

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Zhou

Cui

et al. 2019

Oncol Lett

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Long non-coding RNA-oncogene-induced senescence 1 (lncRNA-OIS1) is a novel lncRNA that is involved in oncogene-induced senescence, while its functionality in cervical squamous cell carcinoma is unknown. In the present study, 68 human papillomavirus (HPV)-positive and 22 HPV-negative patients with cervical squamous cell carcinoma were recruited. Additionally, 40 healthy females were employed as healthy controls. Tumor tissues and adjacent healthy tissues were collected from all patients with cervical squamous cell carcinoma, and blood samples were obtained. Expression of OIS1 was detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of OIS1 for cervical squamous cell carcinoma. HPV-positive and HPV-negative cervical squamous cell carcinoma and normal cervical cell lines were used, and the effects of OIS1 or mitogen-activated protein kinase kinase kinase 4, (MTK-1) expression vector transfection on the proliferation of cell lines and MTK-1 expression were detected by CCK-8 assay and western blotting, respectively. It was established that a reduction in OIS1 expression level in tumor tissues was apparent only in HPV-positive patients. Serum levels of OIS1 were lower in HPV-positive patients compared with that in HPV-negative patients and healthy controls, and no significant differences were observed between HPV-negative patients and healthy controls. Serum levels of OIS1 were significantly associated with tumor size, but not distant tumor metastasis. OIS1 expression level was lower in HPV-positive cancer cell lines compared with that in HPV-negative cancer cell lines, while no significant differences were observed between HPV-positive and HPV-negative normal cell lines. OIS1 overexpression inhibited and MTK-1 overexpression promoted the proliferation of HPV-positive, but not HPV-negative cancer or normal cell lines. OIS1 transfection also decreased the expression of MTK-1 in HPV-positive cancer cell lines, but not in any of the other cell lines. Therefore, it was concluded that OIS1 inhibited HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

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Section: Discussioncontrasting

confidence: 62%

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Zhou

Cui

et al. 2019

Oncol Lett

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“…Recent findings indicate that denervation, immobilization, cancer cachexia, chronic kidney disease, fasting, and aging affect the expression of Pvt1, lncMUMA, Atrolnc-1, and MAR1 lncRNAs in the skeletal muscles [48][49][50][51]. In addition, the expression of Myoparr and Chronos is increased by surgical denervation and aging, respectively, and regulates skeletal muscle mass through BMP signaling [35,52], which antagonizes muscle atrophy [53,54]. Other lncRNAs, namely AK017368, Charme, and lnc-mg, are also involved in the regulation of skeletal muscle mass through multiple mechanisms [55][56][57].…”

Section: Discussionmentioning

confidence: 99%

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

Hitachi

Nakatani

Funasaki

et al. 2020

IJMS

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Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

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“…Analogously to Mhrt, in skeletal muscle cells, the Gm17281 lncRNA, known as Chronos, inhibits hypertrophy through the Bmp7 signaling. Mechanistically, Chronos acts as an epigenetic repressor of Bmp7 cascade through the recruitment of EZH2 on the Bmp7 promoter (Neppl et al, 2017). In murine cardiac fibroblasts, a microarray analysis led to the identification of several lncRNAs dysregulated after pressure overload upon TAC.…”

Section: Nuclear-enriched Lncrnasmentioning

confidence: 99%

Non-coding RNAs Shaping Muscle

Martone

Mariani

Desideri

et al. 2020

Front. Cell Dev. Biol.

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In 1957, Francis Crick speculated that RNA, beyond its protein-coding capacity, could have its own function. Decade after decade, this theory was dramatically boosted by the discovery of new classes of non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and circular RNAs (circRNAs), which play a fundamental role in the fine spatio-temporal control of multiple layers of gene expression. Recently, many of these molecules have been identified in a plethora of different tissues, and they have emerged to be more cell-type specific than protein-coding genes. These findings shed light on how ncRNAs are involved in the precise tuning of gene regulatory mechanisms governing tissues homeostasis. In this review, we discuss the recent findings on the mechanisms used by lncRNAs and circRNAs to sustain skeletal and cardiac muscle formation, paying particular attention to the technological developments that, over the last few years, have aided their genome-wide identification and study. Together with lncRNAs and circRNAs, the emerging contribution of Piwi-interacting RNAs and transfer RNA-derived fragments to myogenesis will be also discussed, with a glimpse on the impact of their dysregulation in muscle disorders, such as myopathies, muscle atrophy, and rhabdomyosarcoma degeneration.

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lncRNA Chronos is an aging-induced inhibitor of muscle hypertrophy

Abstract: Neppl et al. identify a long noncoding RNA named Chronos whose expression increases with age and decreases in Akt-mediated growth. Inhibition of Chronos induces myofiber hypertrophy in vitro and in vivo, in part, through the epigenetic modulation of Bmp7 signaling.

Cited by 44 publications

References 39 publications

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

Non-coding RNAs Shaping Muscle

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