长非编码 RNA ROR 招募组蛋白甲基转移酶 MLL1 上调 TIMP3 表达并促进乳腺癌进展。
Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression.
机构信息
Department of Pathology, Henan Provincial People's Hospital, No. 7, Weiwu Road, Zhengzhou, 450003, Henan, People's Republic of China.
Henan University People's Hospital, Zhengzhou, 450003, People's Republic of China.
出版信息
J Transl Med. 2021 Mar 2;19(1):95. doi: 10.1186/s12967-020-02682-5.
BACKGROUND
As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer.
METHODS
RT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells. MCF-7 cells were subsequently introduced with oe-lncRNA ROR, sh-lncRNA ROR to explore the effects of lncRNA ROR on cell proliferation, invasion and apoptosis.
RESULTS
RIP, RNA pull-down and ChIP assays provided evidence suggesting that lncRNA ROR recruited transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription. The rescue experiments demonstrated that lncRNA ROR knockdown could inhibit the progression of breast cancer via the downregulation of TIMP3. Finally, the in vivo experiment findings consistently highlighted the suppressive effects of lncRNA ROR silencing on tumor growth.
CONCLUSION
Taken together, our study demonstrates that silencing of lncRNA ROR inhibits breast cancer progression via repression of transmethylase MLL1 and TIMP3, emphasizing the potential of lncRNA ROR as a novel target against breast cancer.
背景
乳腺癌作为全球癌症死亡的重要原因，仍然是一种棘手的恶性肿瘤。长链非编码 RNA（lncRNA）被认为与乳腺癌的发生发展有关。异常甲基化与不良的乳腺癌预后相关。本研究旨在阐明 lncRNA ROR 在乳腺癌中的作用。
方法
采用 RT-qPCR 检测乳腺癌组织中 lncRNA ROR 是否高表达，检测乳腺癌细胞中 lncRNA ROR 的核质表达。随后在 MCF-7 细胞中转染 oe-lncRNA ROR、sh-lncRNA ROR，探讨 lncRNA ROR 对细胞增殖、侵袭和凋亡的影响。
结果
RIP、RNA 下拉和 ChIP 实验结果表明，lncRNA ROR 募集转甲基酶 MLL1 促进 H3K4 三甲基化，从而增强 TIMP3 转录。挽救实验表明，lncRNA ROR 敲低可通过下调 TIMP3 抑制乳腺癌的进展。最后，体内实验结果一致强调了沉默 lncRNA ROR 对肿瘤生长的抑制作用。
结论
综上所述，本研究表明沉默 lncRNA ROR 通过抑制转甲基酶 MLL1 和 TIMP3 抑制乳腺癌的进展，强调了 lncRNA ROR 作为一种新型乳腺癌治疗靶点的潜力。
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