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GALNT6基因敲低抑制结肠癌细胞的增殖和迁移并增加癌细胞对5-氟尿嘧啶的敏感性。

GALNT6 Knockdown Inhibits the Proliferation and Migration of Colorectal Cancer Cells and Increases the Sensitivity of Cancer Cells to 5-FU.

作者信息

Peng Xiangdong, Chen Xueru, Zhu Xiuting, Chen Ling

机构信息

Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.

Department of Gynaecology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.

出版信息

J Cancer. 2021 Oct 30;12(24):7413-7421. doi: 10.7150/jca.62332. eCollection 2021.

Abstract

The incidence of colorectal cancer (CRC) is increasing annually worldwide, highlighting the need for novel therapeutics to be developed. GALNT6 is a member of the N-acetylgalactosyltransferase enzyme family, which exhibits oncogenic functions in several types of cancers, such as breast cancer and ovarian cancer. However, the function of GALNT6 in CRC has not received much attention in recent years and is therefore poorly understood. In this study, the GALNT6 gene was screened using RNA-seq data obtained from The Cancer Genome Atlas (TCGA). RNA-seq data from 50 pairs of matched CRC patients in TCGA were obtained and analyzed, and the protein expression levels of GALNT6 were verified in 10 pairs of clinical samples. These samples showed that GALNT6 was highly expressed in CRC tissues. Functional analysis also showed that GALNT6 knockdown inhibited the proliferation and migration of CRC cells and increased the number of apoptotic cells. Furthermore, GALNT6 knockdown suppressed tumor growth . GALNT6 also regulated the AKT pathway based on ingenuity pathway analysis and western blotting assay. Finally, GALNT6 knockdown was observed to increase the sensitivity of CRC cells to 5-Fluorouracil (5-FU). These results, taken together, show that GALNT6 knockdown inhibits proliferation and migration of CRC cells and increases cellular sensitivity to 5-FU. It is therefore possible that targeting GALNT6 might prove to be an effective avenue for exploration in any attempt to develop new therapies for the treatment of CRC.

摘要

全球范围内,结直肠癌(CRC)的发病率逐年上升,这凸显了开发新型治疗方法的必要性。GALNT6是N-乙酰半乳糖基转移酶家族的成员,在乳腺癌和卵巢癌等多种癌症中发挥致癌作用。然而,近年来GALNT6在CRC中的功能并未受到太多关注,因此人们对其了解甚少。在本研究中,利用从癌症基因组图谱(TCGA)获得的RNA测序数据筛选GALNT6基因。获取并分析了TCGA中50对匹配的CRC患者的RNA测序数据,并在10对临床样本中验证了GALNT6的蛋白表达水平。这些样本显示GALNT6在CRC组织中高表达。功能分析还表明,敲低GALNT6可抑制CRC细胞的增殖和迁移,并增加凋亡细胞的数量。此外,敲低GALNT6可抑制肿瘤生长。基于 Ingenuity 通路分析和蛋白质免疫印迹分析,GALNT6还调节AKT通路。最后,观察到敲低GALNT6可增加CRC细胞对5-氟尿嘧啶(5-FU)的敏感性。综上所述,这些结果表明,敲低GALNT6可抑制CRC细胞的增殖和迁移,并增加细胞对5-FU的敏感性。因此,靶向GALNT6可能是开发CRC新疗法的有效探索途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0293/8734422/78ded4cbceee/jcav12p7413g001.jpg

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