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长非编码 RNA RHPN1-AS1 通过作为 ceRNA 对抗 miR-596 并上调 LETM1 促进卵巢癌的发生和转移。

Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1.

机构信息

Department of Laboratory Medicine, Wenling Maternal and Child Health Care Hospital, Wenling 317500, Zhejiang Province, China.

Department of Obstetrics and Gynecology, Wenling Maternal and Child Health Care Hospital, Wenling 317500, Zhejiang Province, China.

出版信息

Aging (Albany NY). 2020 Mar 12;12(5):4558-4572. doi: 10.18632/aging.102911.

DOI:10.18632/aging.102911
PMID:32163372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7093190/
Abstract

BACKGROUND

In recent decades, long non-coding RNAs (lncRNAs) have been reported as crucial functional regulators involved in ovarian cancer. In the present study, we explored how lncRNA RHPN1-AS1 influences the progression of epithelial ovarian cancer (EOC) through tumor cell-dependent mechanisms.

RESULTS

The expression of RHPN1-AS1 in EOC tissues was higher than that in para-cancerous control tissues. High expression of RHPN1-AS1 was closely associated with poor prognosis in EOC patients. N6-methyladenosine (m6A) improved the stability of RHPN1-AS1 methylation transcript by reducing RNA degradation, which resulted in upregulation of RHPN1-AS1 in EOC. In vitro and in vivo functional experiments showed that RHPN1-AS1 promoted EOC cell proliferation and metastasis. RHPN1-AS1 acted as a ceRNA to sponge miR-596, consequently increasing LETM1 expression and activating the FAK/PI3K/Akt signaling pathway.

CONCLUSION

RHPN1-AS1-miR-596-LETM1 axis plays a crucial role in EOC progression. Our findings may provide promising drug targets for EOC treatment.

METHODS

We determined the aberrantly expressed lncRNAs in EOC via microarray analysis and validated RHPN1-AS1 expression by qRT-PCR. The RHPN1-AS1-miR-596-LETM1 axis was examined by dual-luciferase reporter assay and RIP assay. The mechanism of RHPN1-AS1 was investigated through gain- and loss-of-function studies both in vivo and in vitro.

摘要

背景

近几十年来，长链非编码 RNA（lncRNA）已被报道为参与卵巢癌的关键功能调控因子。在本研究中，我们通过肿瘤细胞依赖的机制探索了 lncRNA RHPN1-AS1 如何影响上皮性卵巢癌（EOC）的进展。

结果

EOC 组织中 RHPN1-AS1 的表达高于癌旁对照组织。RHPN1-AS1 的高表达与 EOC 患者的不良预后密切相关。N6-甲基腺苷（m6A）通过减少 RNA 降解来提高 RHPN1-AS1 甲基化转录物的稳定性，从而导致 EOC 中 RHPN1-AS1 的上调。体外和体内功能实验表明，RHPN1-AS1 促进 EOC 细胞的增殖和转移。RHPN1-AS1 作为 ceRNA 可海绵吸附 miR-596，从而增加 LETM1 的表达并激活 FAK/PI3K/Akt 信号通路。

结论

RHPN1-AS1-miR-596-LETM1 轴在 EOC 进展中起着关键作用。我们的研究结果可能为 EOC 的治疗提供有前景的药物靶点。

方法

我们通过微阵列分析确定了 EOC 中异常表达的 lncRNA，并通过 qRT-PCR 验证了 RHPN1-AS1 的表达。通过双荧光素酶报告基因检测和 RIP 实验检测 RHPN1-AS1-miR-596-LETM1 轴。通过体内和体外的功能增益和缺失研究来研究 RHPN1-AS1 的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/97f834674eee/aging-12-102911-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/c0eaac71d9bd/aging-12-102911-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/1be66839d6f1/aging-12-102911-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/779f53fd5a89/aging-12-102911-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/b1afea8fd981/aging-12-102911-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/64f2d4007224/aging-12-102911-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/97f834674eee/aging-12-102911-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/c0eaac71d9bd/aging-12-102911-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/1be66839d6f1/aging-12-102911-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/779f53fd5a89/aging-12-102911-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/71d443c3b3cf/aging-12-102911-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/64f2d4007224/aging-12-102911-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a14b/7093190/97f834674eee/aging-12-102911-g007.jpg

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