Department of General Surgery, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
J Cell Physiol. 2019 Dec;234(12):22343-22351. doi: 10.1002/jcp.28800. Epub 2019 May 8.
Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13-AS) has been found as an oncogene in many cancers; however, the role of HOXC13-AS in breast cancer still elusive. In this study, the HOXC13-AS levels and its role in cell proliferation was first measured by real-time quantitative polymerase chain reaction, Cell Counting Kit-8 assay, and colony formation assay. It showed that HOXC13-AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13-AS promoted the growth of breast cancer cells. Then, we found that the miR-497-5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR-497-5p suppressed breast cancer cell proliferation. Further study showed that HOXC13-AS could function as a "sponge" for miR-497-5p then suppress miR-497-5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR-497-5p. Overexpression of miR-497-5p by chemical mimics decreased the expression of PTEN, while downregulation of miR-497-5p by HOXC13-AS rescued the expression of PTEN. Finally, we showed that HOXC13-AS promoted the proliferation of breast cancer cells and tumor growth through miR-497-5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13-AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR-497-5p and further upregulated PTEN.
失调的长非编码 RNA(lncRNA)在肿瘤发生中仍有待探索。LncRNA HOXC13 反义 RNA(HOXC13-AS)已在许多癌症中被发现为癌基因;然而,HOXC13-AS 在乳腺癌中的作用仍不清楚。在这项研究中,首先通过实时定量聚合酶链反应、细胞计数试剂盒-8 测定和集落形成测定来测量 HOXC13-AS 的水平及其在细胞增殖中的作用。结果表明,与相邻正常组织相比,乳腺癌组织中 HOXC13-AS 水平升高,上调的 HOXC13-AS 促进了乳腺癌细胞的生长。然后,我们发现与相邻组织相比,癌症组织中的 miR-497-5p 水平下调,miR-497-5p 抑制乳腺癌细胞增殖。进一步的研究表明,HOXC13-AS 可以作为 miR-497-5p 的“海绵”,从而抑制 miR-497-5p 的表达。此外,我们接下来确定磷酸酶和张力蛋白同源物(PTEN)是 miR-497-5p 的靶标。化学模拟物过表达 miR-497-5p 可降低 PTEN 的表达,而 HOXC13-AS 下调 miR-497-5p 可挽救 PTEN 的表达。最后,我们表明 HOXC13-AS 通过 miR-497-5p/PTEN 轴在体外和体内促进了乳腺癌细胞的增殖和肿瘤生长。因此,我们得出结论,HOXC13-AS 在乳腺癌中显著上调,通过抑制 miR-497-5p 进一步上调 PTEN 促进细胞增殖。