LINC00473/miR-374a-5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy
LINC00473/miR-374a-5p regulates esophageal squamous cell carcinoma via targeting SPIN1 to weaken the effect of radiotherapy
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DOI：
10.1002/jcb.28717
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发表时间：
2019-09-01
影响因子：
4
通讯作者：
Li, Chao
中科院分区：
文献类型：
--
作者：
Chen, Weizuo;Zhang, Yanshan;Li, Chao
食管鳞状细胞癌（ESCC）是食管癌中最常见的类型。尽管食管鳞癌的治疗取得了一定的进展，但由于治疗失败，患者仍会复发，其中一个原因就是放射抵抗。因此，有必要探讨食管鳞癌放射抵抗的分子机制。已报道长基因间非编码RNA 473（LINC 00473）在几种人类恶性肿瘤中异常表达。然而，其在食管鳞癌放射敏感性中的生物学功能仍有待充分了解。本研究探讨LINC 00473在食管鳞癌细胞辐射敏感性中的作用，以及LINC 00473是否作为竞争性内源性RNA来实现其对辐射抗性的调节。我们发现LINC 00473在食管鳞癌组织和细胞系中显著上调，并且其表达与细胞对辐射的反应显著相关。此外，LINC 00473的敲低可使ESCC细胞对体外辐射敏感。至于潜在的机制，我们发现LINC 00473和miR-374 a-5 p之间存在相互抑制作用。证实Spindlin 1（SPIN 1）是miR-374 a-5 p的下游靶点，LINC 00473通过负调节miR-374 a-5 p表达上调SPIN 1表达。此外，我们发现SPIN 1可以加重食管鳞癌细胞的辐射抗性。最后，SPIN 1的过表达逆转了LINC 00473沉默增强的ESCC细胞的放射敏感性。综上所述，我们证明了LINC 00473通过调节ESCC中的miR-374 a-5 p/SPIN 1轴来促进辐射抗性。
Esophageal squamous cell carcinoma (ESCC) is the most prevalent type in esophageal cancers. Despite accumulating achievements in treatments of ESCC, patients still suffer from recurrence because of the treatment failures, one of the reasons for which is radioresistance. Therefore, it is a necessity to explore the molecular mechanism underlying ESCC radioresistance. Long intergenic noncoding RNA 473 (LINC00473) has been reported to be aberrantly expressed in several human malignancies. However, its biological function in radiosensitivity of ESCC remains to be fully understood. This study explored the role of LINC00473 in radiosensitivity of ESCC cells and whether LINC00473 acted as a competing endogenous RNA to realize its modulation on radioresistance. We found that LINC00473 was markedly upregulated in ESCC tissues and cell lines, and its expression was remarkably related to cellular response to irradiation. In addition, knockdown of LINC00473 could sensitize ESCC cells to radiation in vitro. As for the underlying mechanism, we uncovered that there was a mutual inhibition between LINC00473 and miR-374a-5p. Spindlin1 (SPIN1) was verified as a downstream target of miR-374a-5p, and LINC00473 upregulated SPIN1 expression through negatively modulating miR-374a-5p expression. Furthermore, we revealed that SPIN1 could aggravate the radioresistance of ESCC cells. Finally, overexpression of SPIN1 reversed the LINC00473 silencing-enhanced radiosensitivity in ESCC cells. To sum up, we demonstrated that LINC00473 facilitated radioresistance by regulating the miR-374a-5p/SPIN1 axis in ESCC.