Long Quanyi, Li Hongjiang, Fan Yuan, Zhang Jia
Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu City, Sichuan Province 610041, People's Republic of China.
Cancer Manag Res. 2020 Nov 6;12:11403-11410. doi: 10.2147/CMAR.S258191. eCollection 2020.
Long non-coding RNA (lncRNA) TatD DNase Domain Containing 1 (TATDN1) is a recently characterized oncogenic lncRNA in several types of cancer including breast cancer. Our preliminary microarray analysis revealed its upregulation in triple negative breast cancer (TNBC) and its inverse correlation with microRNA-26b (miR-26b), which is a tumor suppressive miRNA in breast cancer. This study was therefore carried out to investigate the interaction between TATDN1 and miR-26b in TNBC.
A total of 66 pairs of TNBC and non-tumor tissues were collected from 66 patients (45.8 ± 10.5 years old) with TNBC through biopsy under the guidance of MRI before initiation of any therapies. Quantitative reverse transcription PCR (RT-qPCR), transient cell transfection, methylation specific PCR (MSP) and cell proliferation assay were carried out in this study.
We found that TATDN1 was upregulated and miR-26b was downregulated in TNBC. Correlation analysis showed that the expression of TATDN1 and miR-26b was inversely correlated. In TNBC cells, overexpression of TATDN1 mediated the downregulation of miR-26b. Knockdown of TATDN1 led to the upregulation of miR-26b. Methylation-specific PCR showed that TATDN1 positively regulated the methylation of miR-26b gene. Cell proliferation analysis showed that TATDN1 positively regulated the proliferation of TNBC cells. Overexpression of miR-26b attenuated the effects of TATDN1 overexpression on cell proliferation.
Therefore, overexpression of TATDN1 promotes cancer cell proliferation in TNBC by regulating the methylation of miR-26b gene.
长链非编码RNA(lncRNA)含TatD核酸酶结构域1(TATDN1)是一种最近在包括乳腺癌在内的多种癌症中被鉴定出的致癌lncRNA。我们初步的微阵列分析显示其在三阴性乳腺癌(TNBC)中上调,且与微小RNA-26b(miR-26b)呈负相关,miR-26b是乳腺癌中的一种肿瘤抑制性微小RNA。因此,本研究旨在探讨TNBC中TATDN1与miR-26b之间的相互作用。
在开始任何治疗前,通过MRI引导下的活检从66例TNBC患者(年龄45.8±10.5岁)中收集了66对TNBC组织和非肿瘤组织。本研究进行了定量逆转录PCR(RT-qPCR)、瞬时细胞转染、甲基化特异性PCR(MSP)和细胞增殖测定。
我们发现TNBC中TATDN1上调而miR-26b下调。相关性分析表明TATDN1和miR-26b的表达呈负相关。在TNBC细胞中,TATDN1的过表达介导了miR-26b的下调。TATDN1的敲低导致miR-26b上调。甲基化特异性PCR显示TATDN1正向调节miR-26b基因的甲基化。细胞增殖分析表明TATDN1正向调节TNBC细胞的增殖。miR-26b的过表达减弱了TATDN1过表达对细胞增殖的影响。
因此,TATDN1的过表达通过调节miR-26b基因的甲基化促进TNBC中的癌细胞增殖。