Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
J Cell Mol Med. 2019 Apr;23(4):2549-2557. doi: 10.1111/jcmm.14145. Epub 2019 Jan 31.
MiR-4732-5p was previously found to be dysregulated in nipple discharge of breast cancer. However, the expression and function of miR-4732-5p in breast cancer remain largely unknown. Here, the expression of miR-4732-5p was detected using quantitative real-time PCR in breast cancer tissues and cell lines. Cell proliferation, apoptosis, migration and invasion assays were performed to examine the effects of miR-4732-5p in breast cancer. In addition, mRNA sequencing, bioinformatics analysis, Western blot and luciferase assays were performed to identify the target of miR-4732-5p. Overall, miR-4732-5p was significantly down-regulated in breast cancer tissues, especially in lymph node metastasis (LNM)-negative tissues, compared with adjacent normal tissues. However, it was more highly expressed in LNM-positive breast cancer tissues, compared with LNM-negative ones. Expression of miR-4732-5p was positively correlated with lymph node metastasis, larger tumour size, advanced clinical stage, high Ki-67 levels and poor prognosis. MiR-4732-5p promoted cell proliferation, migration and invasion in breast cancer. MiR-4732-5p directly targeted the 3'-UTR of tetraspanin 13 (TSPAN13) and suppressed TSPAN13 expression at the mRNA and protein levels. These results suggested that miR-4732-5p may serve as a tumour suppressor in the initiation of breast cancer, but as a tumour promoter in breast cancer progression by targeting TSPAN13.
miR-4732-5p 先前被发现于乳腺癌的乳头溢液中失调。然而，miR-4732-5p 在乳腺癌中的表达和功能仍知之甚少。在此，我们使用实时定量 PCR 检测了乳腺癌组织和细胞系中 miR-4732-5p 的表达。通过细胞增殖、凋亡、迁移和侵袭实验来研究 miR-4732-5p 对乳腺癌的影响。此外，进行了 mRNA 测序、生物信息学分析、Western blot 和荧光素酶报告基因实验来鉴定 miR-4732-5p 的靶基因。总的来说，miR-4732-5p 在乳腺癌组织中，特别是在淋巴结转移（LNM）阴性组织中，与相邻正常组织相比，表达显著下调。然而，在 LNM 阳性乳腺癌组织中，miR-4732-5p 的表达高于 LNM 阴性组织。miR-4732-5p 的表达与淋巴结转移、肿瘤较大、临床分期较晚、Ki-67 水平较高和预后不良呈正相关。miR-4732-5p 促进了乳腺癌细胞的增殖、迁移和侵袭。miR-4732-5p 直接靶向四跨膜蛋白 13（TSPAN13）的 3'UTR，并抑制 TSPAN13 的 mRNA 和蛋白水平的表达。这些结果表明，miR-4732-5p 可能作为乳腺癌发生的肿瘤抑制因子，但通过靶向 TSPAN13 作为肿瘤促进因子参与乳腺癌的进展。
