Department of Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, PR China; Department of General Surgery, Yancheng City No.1 People's Hospital, Yancheng 224000, Jiangsu Province, PR China.
Department of General Surgery, Yancheng City No.1 People's Hospital, Yancheng 224000, Jiangsu Province, PR China.
Cell Signal. 2022 Feb;90:110188. doi: 10.1016/j.cellsig.2021.110188. Epub 2021 Nov 9.
Ubiquitously expressed transcript (UXT) is a prefoldin-like protein. It was reported that UXT played vital role in several cancer types. However, functional role of UXT in breast cancer need further investigation.
mRNA level or protein level of were determined by qRT-PCR or western blots. Proliferation of breast cancer cells was evaluated by CCK-8 assay and EdU assay. Migrative and invasive ability of cells were determined by wound healing assay and transwell assay. Transcriptional activation of UXT was determined by dual luciferase activity. The enrichment of H3K27me3 and EZH2 on the promoter of RND3 was evaluated by ChIP assay. The methylation of RND3 promoter was determined by MSP assay. In vivo function of UXT was evaluated by xenograft model.
Our results indicated that UXT was elevated in breast cancer and associated with poor prognosis. HOXD9 elevated expression of UXT via transcriptional activation. UXT knockdown impaired the proliferation, migration and invasion. Rescue experiments suggested that UXT promoted malignant phenotypes of breast cancer cells via epigenetically repressing RND3. Moreover, UXT promoted tumorigeneses and metastasis of breast cancer cell in vivo.
Inhibition of UXT impaired proliferation and metastasis of cancer cell via promoting RND3. Moreover, UXT epigenetically repressed the expression of RND3 via recruiting EZH2 in the promoter of RND3.
普遍表达转录本（UXT）是一种类原初折叠蛋白。有报道称，UXT 在多种癌症类型中发挥着重要作用。然而，UXT 在乳腺癌中的功能作用仍需进一步研究。
通过 qRT-PCR 或 Western blot 测定 mRNA 水平或蛋白水平。用 CCK-8 法和 EdU 法评估乳腺癌细胞的增殖。用划痕愈合实验和 Transwell 实验测定细胞的迁移和侵袭能力。通过双荧光素酶活性测定 UXT 的转录激活。用 ChIP 实验评估 H3K27me3 和 EZH2 在 RND3 启动子上的富集情况。用 MSP 实验测定 RND3 启动子的甲基化。通过异种移植模型评估 UXT 的体内功能。
我们的结果表明，UXT 在乳腺癌中上调，并与预后不良相关。HOXD9 通过转录激活上调 UXT 的表达。UXT 敲低会损害增殖、迁移和侵袭能力。挽救实验表明，UXT 通过表观遗传抑制 RND3 促进乳腺癌细胞的恶性表型。此外，UXT 在体内促进了乳腺癌细胞的肿瘤发生和转移。
抑制 UXT 通过促进 RND3 来损害癌细胞的增殖和转移。此外，UXT 通过在 RND3 启动子上募集 EZH2 来表观遗传抑制 RND3 的表达。
