子宫内膜异位症恶性转化分子机制的新发现：BANCR 促进 miR-612/CPNE3 通路的活性。

IF 3.7 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online Pub Date : 2024-06-21 DOI:10.1016/j.rbmo.2024.104326

Chang Liu , Peng Chen , Zhuo Yang , Keming Zhang , Fang Chen , Yanmei Zhu , Jing Liu , Liying Liu , Danni Wang , Danbo Wang

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On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between <em>BANCR</em>, miR-612 and <em>CPNE3</em>, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>The expression levels of <em>BANCR</em> and <em>CPNE3</em> were lowest in normal endometrium, significantly increased in eutopic endometrium (<em>P</em> < 0.05) and was significantly increased in eutopic endometrium (<em>P</em> < 0.05). During the malignant transformation of endometriosis, the expression levels of <em>BANCR</em> and CPNE3 were significantly upregulated (<em>P</em> < 0.05), whereas those of miR-612 were significantly downregulated (<em>P</em> < 0.05). miRNA-612 was found to target <em>BANCR</em> and <em>CPNE3</em>. 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引用次数: 0

摘要

研究问题：LncRNA BANCR是否通过激活miR-612/CPNE3通路促进子宫内膜异位症的恶性转化？BANCR、miR-612和CPNE3在正常子宫内膜、子宫内膜异位症异位内膜、异位内膜或子宫内膜异位症相关卵巢癌恶性组织中的表达模式。在原代正常子宫内膜基质细胞（NESC）和异位子宫内膜基质细胞（EESC）的基础上，在体外和体内阐明了 BANCR、miR-612 和 CPNE3 之间的调控关系以及促进子宫内膜异位症恶性转化的潜在机制：BANCR和CPNE3在正常子宫内膜中的表达水平最低，在异位子宫内膜中的表达水平显著升高（P＜0.05），在异位子宫内膜中的表达水平显著升高（P＜0.05）。在子宫内膜异位症恶变过程中，BANCR 和 CPNE3 的表达水平明显上调（P < 0.05），而 miR-612 的表达水平明显下调（P < 0.05）。BANCR 在 NESC 和 EESC 中的过表达和敲除分别上调和下调了 CPNE3 的表达，并促进或阻止了细胞的增殖和迁移；这些效应被 miR-612 模拟物和抑制剂逆转。这些变化均有统计学意义（P < 0.05）。体内实验显示，BANCR通过调节miR-612/CPNE3显著提高了皮下子宫内膜细胞的存活率（P < 0.05）：结论：BANCR的表达随着子宫内膜异位症恶变过程的进展而逐渐增加，并通过miR-612/CPNE3途径促进子宫内膜细胞的增殖和迁移。BANCR可能是监测子宫内膜异位症恶性转化的一个新靶点。

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New insights into molecular mechanisms underlying malignant transformation of endometriosis: BANCR promotes miR-612/CPNE3 pathway activity

Research question

Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway?

Design

The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo.

Results

The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05).

Conclusion

The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.

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来源期刊

Reproductive biomedicine online 医学-妇产科学

CiteScore

7.20

自引率

7.50%

发文量

391

审稿时长

50 days

期刊介绍： Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients. Context: The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.