Teoh Seong Lin, Das Srijit
Department of Anatomy, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Kuala Lumpur, Malaysia.
Tumour Biol. 2016 Nov;37(11):14363-14380. doi: 10.1007/s13277-016-5357-7. Epub 2016 Sep 14.
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
肥胖仍然是一个重大的全球性问题。多种癌症与肥胖有关,正确理解其病因,尤其是分子肿瘤生物学,对于早期诊断和更好的治疗至关重要。基因在肥胖的发生发展中起着重要作用。少数基因如瘦素、由db(糖尿病)编码的瘦素受体、阿黑皮素原、AgRP和NPY以及黑皮质素-4受体和胰岛素诱导基因2与肥胖有关。微小RNA通过mRNA降解和抑制蛋白质翻译来控制基因表达,并影响细胞分化、细胞生长和细胞死亡。miR-143的过表达通过抑制B细胞淋巴瘤2、细胞外信号调节激酶-5活性和KRAS癌基因来抑制肿瘤生长。乳腺癌、子宫癌、肾癌、甲状腺癌和肝癌也与肥胖有关。性激素和胰岛素产生的任何紊乱都会导致细胞增殖、分化和凋亡之间的平衡失调。肥胖与癌症之间的可能机制涉及脂肪因子和性激素水平的改变。这些介质作为癌症进展的生物标志物,同时也是癌症治疗和预防的靶点。有趣的是,许多抗癌药物对治疗肥胖也有益,反之亦然。我们还综述了少数对癌症和肥胖都有作用的药物在机制上的可能联系。本综述可能对分子生物学家、肿瘤学家和治疗癌症的临床医生具有重要意义,也为更好的治疗选择铺平了道路。