Long noncoding RNA PCAT1, a novel serum-based biomarker, enhances cell growth by sponging miR-326 in oesophageal squamous cell carcinoma
Long noncoding RNA PCAT1, a novel serum-based biomarker, enhances cell growth by sponging miR-326 in oesophageal squamous cell carcinoma
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DOI：
10.1038/s41419-019-1745-4
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发表时间：
2019-07-04
影响因子：
9
通讯作者：
Liu, Xuefeng
中科院分区：
文献类型：
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作者：
Huang, Lijie;Wang, Yan;Liu, Xuefeng
长链非编码RNA（lncRNA）在人类癌症的发生和进展中发挥着重要作用。据报道，lncRNA 前列腺癌相关转录物 1 (PCAT1) 与多种人类癌症有关，包括食管鳞状细胞癌 (ESCC)。然而，PCAT1 在 ESCC 中的详细生物学功能、潜在机制和临床相关性仍不清楚。在这里，我们证实 PCAT1 在 ESCC 组织和细胞系中高表达。 PCAT1 的敲低抑制了 ESCC 细胞的生长，而 PCAT1 的过表达在体外和体内均显示出相反的效果。此外，PCAT1的敲低使细胞周期停滞在G2/M期，减少细胞周期蛋白B1和CDC2的表达，并使细胞对紫杉醇更加敏感。此外，PCAT1 可以与多种人类癌症中的肿瘤抑制因子 miR-326 结合。拯救实验表明，miR-326 的强制表达减弱了 PCAT1 对 ESCC 细胞生长的促进作用。此外，我们发现PCAT1存在于ESCC细胞来源的外泌体中，且在ESCC患者的血清中含量高于健康志愿者捐赠者，并通过外泌体促进细胞生长。因此，我们的数据表明，PCAT1 通过海绵 miR-326 促进 ESCC 细胞增殖，并可作为 ESCC 的非侵入性生物标志物。
Long noncoding RNAs (lncRNAs) play important roles in the development and progression of human cancers. The lncRNA prostate cancer-associated transcript 1 (PCAT1) has been reported to be involved in multiple human cancers, including oesophageal squamous cell carcinoma (ESCC). However, the detailed biological functions, underlying mechanisms and clinical relevance of PCAT1 in ESCC remain unclear. Here, we confirmed that PCAT1 was highly expressed in ESCC tissues and cell lines. Knockdown of PCAT1 inhibited the growth of ESCC cells, whereas overexpression of PCAT1 showed the opposite effect both in vitro and in vivo. Moreover, knockdown of PCAT1 arrested the cell cycle at G2/M phase, reduced the expression of cyclin B1 and CDC2, and caused cells to be more sensitive to paclitaxel. Furthermore, PCAT1 could bind to miR-326, a tumour suppressor in diverse human cancers. Rescue experiments revealed that enforced expression of miR-326 attenuated the promotive effect of PCAT1 on ESCC cell growth. In addition, we discovered that PCAT1 was present in ESCC cell-derived exosomes, was higher in the serum of ESCC patients than those of healthy volunteer donors, and promoted cell growth through exosomes. Thus, our data indicate that PCAT1 promotes ESCC cell proliferation by sponging miR-326 and may serve as a non-invasive biomarker for ESCC.