Circulating Small Non-coding RNAs as Biomarkers for Recovery After Exhaustive or Repetitive Exercise

Abstract

Circulating microRNAs have proven to be reliable biomarkers, due to their high stability, both in vivo in the circulation, and ex vivo during sample preparation and storage. Small nucleolar RNAs (snoRNAs) are a different type of small non-coding RNAs that can also be reliably measured in plasma, but have only been studied sporadically. In this study, we aimed to identify RNA-biomarkers that can distinguish between different exercise regimes and that entail clues about muscle repair and recovery after prolonged exhaustive endurance exercise. We compared plasma microRNA profiles between two cohorts of elite cyclists, subjected to two different types of exercise regimes, as well as a cohort of patients with peripheral artery disease (PAD) that were scheduled to undergo lower limb amputation, due to critical limb ischemia. In elite athletes, muscle tissue recovers quickly even after exhaustive exercise, whereas in PAD patients, recovery is completely impaired. Furthermore, we measured levels of a specific group of snoRNAs in the plasma of both elite cyclists and PAD patients. Using a multiplex qPCR screening, we detected a total of 179 microRNAs overall, of which, on average, 161 microRNAs were detected per sample. However, only 30 microRNAs were consistently expressed in all samples. Of these, two microRNAs, miR-29a-3p and miR193a-5p, that responded differently two different types of exercise, namely exhaustive exercise and non-exhaustive endurance exercise. Using individual rt/qPCR, we also identified a snoRNA, SNORD114.1, which was significantly upregulated in plasma in response to endurance exercise. Furthermore, two microRNAs, miR-29a-3p and miR-495-3p, were significantly differentially expressed in athletes compared to PAD patients, but only following exercise. We suggest that these two microRNAs could function as markers of impaired muscle repair and recovery. In conclusion, microRNAs miR-29a-3p and miR-193a-5p may help us distinguish between repeated exhaustive and non-exhaustive endurance exercise. MicroRNA miR-29a-3p, as well as miR-495-3p, may further mark impaired muscle recovery in patients with severe critical limb ischemia. Furthermore, we showed for the first time that a circulating snoRNA, SNORD114.1, is regulated in response to exercise and may be used as biomarker.

Expression signature of six‐snoRNA serves as novel non‐invasive biomarker for diagnosis and prognosis prediction of renal clear cell carcinoma

“…[11][12][13] The defects in ribosome maturation and function can destroy important protein synthesis processes and lead to diseases, especially cancer. 1 18 Despite the emerging knowledge about the role of snoRNAs in cancer, the clinical relevance of snoRNAs in ccRCC has not been investigated systematically. SNORA42, 15 SNORD33, SNORD66, SNORD76, 16 SNORD78 17 and SNORD114.…”

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model

“…micro RNAs (miRNA) are small, 19-25 mer regulator molecules. Interestingly, miRNAs can behave either as oncogenes (oncomirs) or tumor suppressors according to which target mRNA they regulate 19,20 . The comparison of cancer and healthy cells originating from the same tissue presents differences in the expression patterns of miRNA.…”

Plasma Levels of snoRNAs are Associated with Platelet Activation in Patients with Peripheral Artery Disease

“…We previously published that the expression of SNORD112, SNORD113.2 and SNORD113.6 was significantly higher in PAD patients with critical ischemia than in healthy controls [9]. While plasma levels were generally around the detection limit in controls, all four snoRNAs were abundantly expressed in PAD patients with critical ischemia.…”

“…However, microRNAs are not the only small ribonucleic acids (RNAs) that display such favourable properties for biomarkers. We recently showed that a set of small nucleolar RNAs (snoRNAs) had potential as biomarkers for muscle damage and repair in elite athletes and end stage PAD patients [9], as well as for the recovery of patients with ST-elevation myocardial infarction (STEMI) that underwent percutaneous coronary intervention (PCI) [10]. SnoRNAs are also small RNA molecules that are between 60 and 300 nucleotides in length and play an important role in cellular machinery.…”

“…In the current study, we measured four snoRNAs in 104 consecutive PAD patients who underwent elective infrainguinal angioplasty with stent implantation. We selected snoRNAs that showed significant overexpression in the plasma of end-stage PAD patients compared to healthy individuals in a previous study [9]. All four snoRNAs are transcribed from the 14q32 locus, a noncoding RNA gene locus that is strongly linked to human cardiovascular disease, including PAD and restenosis [10,12,13,14,15,16].…”