Gomes João Lucas Penteado, Tobias Gabriel Cardial, Fernandes Tiago, Silveira André Casanova, Negrão Carlos Eduardo, Chammas Roger, Brum Patrícia Chakur, Oliveira Edilamar Menezes
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil.
Heart Institute (InCor), Medical School, University of Sao Paulo, Sao Paulo 05508-030, Brazil.
Cancers (Basel). 2021 Nov 16;13(22):5728. doi: 10.3390/cancers13225728.
We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.
我们研究了氨基乙磺酸(AET)对结肠癌恶病质(CT26)和乳腺癌非恶病质(MMTV-PyMT)癌症小鼠模型骨骼肌和血清中肌微RNA(myomiRs)表达的影响。结肠癌降低了胫骨前肌(TA)中微小RNA-486的表达,增加了PTEN,降低了PI3K/mTOR蛋白通路、身体和肌肉消耗、纤维横截面积以及肌肉功能障碍,而AET无法改善这些情况。相比之下,乳腺癌降低了这些肌肉功能,但AET可使其得到改善。在循环系统中,结肠癌中微小RNA-486和-206的下调,以及乳腺癌中微小RNA-486的下调和微小RNA-206表达的上调可能是良好的癌症血清生物标志物。由于微小RNA-206是骨骼肌特异性的,其在MMTV小鼠的TA、血清和肿瘤中的表达增加,表明这三个部位之间存在交流。AET可防止对MMTV小鼠微小RNA-206的这些影响,但不能防止对微小RNA-486的影响。总之,癌症导致CT26和MMTV小鼠TA和血清中微小RNA-486表达下调,且AET无法预防这些影响;然而,对于MMTV小鼠,训练后的肌肉功能得以保留,可能是由微小RNA-206表达下调维持的。血清微小RNA-206是结肠癌(降低)和乳腺癌(升高)监测疾病进展及AET促进效果的潜在生物标志物。