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肥胖、结直肠癌与 MACC1 表达:一种可能的新分子关联。

Obesity, colorectal cancer and MACC1 expression: A possible novel molecular association.

机构信息

Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle‑Wittenberg, D‑06108 Halle (Saale), Germany.

Max‑Delbrück‑Center for Molecular Medicine in The Helmholtz Association, Molecular Epidemiology Research Group, D‑13125 Berlin, Germany.

出版信息

Int J Oncol. 2022 Feb;60(2). doi: 10.3892/ijo.2022.5307. Epub 2022 Jan 11.

Abstract

Obesity is a major and increasing public health concern, associated with an increased risk of and mortality from several types of cancer including colorectal cancer (CRC), being associated with cancer progression, metastasis and resistance to therapy. It was hypothesized that the expression of cancer/metastasis‑inducing gene metastasis‑associated in colon cancer 1 (MACC1) is increased in obesity, which may constitute a link to obesity‑induced cancer. The present study thus analyzed circulating cell‑free plasma MACC1 expression levels in human obese (vs. normal weight) adult individuals from independent studies, namely the Martin Luther University (MLU) study (n=32) and the Metabolic syndrome study (MetScan, Berlin) (n=191). Higher plasma MACC1 levels were found in obese individuals, increasing with a greater body fat mass and body mass index; these levels were predominantly observed in male and to a lesser extent in female individuals, although the results were not significant. A reduction in body fat mass following dietary intervention and physical exercise decreased the MACC1 expression levels in the MLU study. Furthermore, Wistar rats with diet‑induced obesity exhibited slightly increased plasma MACC1 levels compared with rats of normal weight. The obese Wistar rats exposed to azoxymethane to induce colon cancer exhibited a more severe colon tumor outcome, which was associated with significantly increased MACC1 levels compared with their non‑obese littermates. On the whole, the findings of the present study suggest an association between MACC1 and obesity, as well as with obesity‑induced CRC.

摘要

肥胖是一个主要且日益严重的公共健康问题,与几种类型的癌症(包括结直肠癌)的风险增加和死亡率相关,与癌症的进展、转移和对治疗的耐药性相关。有人假设,结肠癌转移相关基因 1(MACC1)在肥胖中的表达增加,这可能构成肥胖引起癌症的一个联系。因此,本研究分析了来自独立研究的人类肥胖(与正常体重相比)成年个体的循环无细胞血浆 MACC1 表达水平,即马丁路德大学(MLU)研究(n=32)和代谢综合征研究(MetScan,柏林)(n=191)。肥胖个体的血浆 MACC1 水平较高,随着体脂肪量和体重指数的增加而增加;这些水平主要在男性中观察到,在女性中观察到的程度较小,尽管结果不显著。在 MLU 研究中,通过饮食干预和体育锻炼减少体脂肪量降低了 MACC1 的表达水平。此外,与正常体重的大鼠相比,饮食诱导肥胖的 Wistar 大鼠的血浆 MACC1 水平略有升高。暴露于诱导结肠癌的氧化偶氮甲烷的肥胖 Wistar 大鼠表现出更严重的结肠肿瘤结局,与非肥胖同窝仔鼠相比,其 MACC1 水平显著升高。总体而言,本研究的结果表明 MACC1 与肥胖以及肥胖诱导的结直肠癌之间存在关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/793a/8776326/dde43a019800/IJO-60-02-05307-g00.jpg

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