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长链非编码 RNA HOTTIP 通过调节 miR-615-3p/SMARCE1 通路促进卵巢癌的转移潜能。

Long noncoding RNA HOTTIP promotes the metastatic potential of ovarian cancer through the regulation of the miR-615-3p/SMARCE1 pathway.

机构信息

Department of Obstetrics, Weifang Maternal and Child Health Hospital, Weifang, Shandong, China.

出版信息

Kaohsiung J Med Sci. 2020 Dec;36(12):973-982. doi: 10.1002/kjm2.12282. Epub 2020 Aug 12.

Abstract

Upregulation of lncRNA HOXA transcript at the distal tip (HOTTIP) plays important roles in cancer progression. Nevertheless, its functions in the growth and metastasis of ovarian carcinoma are unknown. In this study, we demonstrated overexpression of HOTTIP in ovarian cancer cell lines and clinical tissues. Further, we showed that higher level of HOTTIP was associated with poor survival of ovarian cancer patients. Notably, HOTTIP silencing restrained proliferation, migration, and invasiveness of ovarian carcinoma cells. On the other hand, upregulation of HOTTIP remarkably exacerbated the aggressive traits of ovarian carcinoma cells. In addition, HOTTIP served as a sponge of miR-615-3p to upregulate SMARCE1 level. Further, upregulation of miR-615-3p or downregulation of SMARCE1 reversed the carcinogenic impacts of HOTTIP in ovarian cancer. HOTTIP and miR-615-3p expression levels in ovarian cancer cells were negatively correlated, whereas HOTTIP and SMARCE1 expression levels were positively correlated. In nude mice, downregulation of HOTTIP reduced cell growth in vivo. In summary, lncRNA HOTTIP promotes the growth and metastatic phenotypes of ovarian cancer via regulating miR-615-3p/SMARCE1 pathway.

摘要

长链非编码 RNA HOXA 转录物远端末端(HOTTIP)的上调在癌症进展中发挥重要作用。然而,其在卵巢癌生长和转移中的功能尚不清楚。在这项研究中,我们证明了 HOTTIP 在卵巢癌细胞系和临床组织中的过表达。此外,我们表明 HOTTIP 水平较高与卵巢癌患者的生存不良有关。值得注意的是,HOTTIP 沉默抑制了卵巢癌细胞的增殖、迁移和侵袭。另一方面,HOTTIP 的上调显著加剧了卵巢癌细胞的侵袭特性。此外,HOTTIP 作为 miR-615-3p 的海绵,上调了 SMARCE1 水平。此外,上调 miR-615-3p 或下调 SMARCE1 逆转了 HOTTIP 在卵巢癌中的致癌作用。卵巢癌细胞中 HOTTIP 和 miR-615-3p 的表达水平呈负相关,而 HOTTIP 和 SMARCE1 的表达水平呈正相关。在裸鼠中,下调 HOTTIP 减少了体内细胞的生长。总之,长链非编码 RNA HOTTIP 通过调节 miR-615-3p/SMARCE1 通路促进卵巢癌的生长和转移表型。

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