Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression

Abstract

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.

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

“…The recruitment of SUV39H1 triggers H3K9 methylation of human hyaluronidase family member PH20 and inhibits breast cancer growth and metastasis [ 103 ]. Being overexpressed in breast cancer tissues, lncRNA ROR promotes breast cancer progression via repression of transmethylase mixed-lineage leukemia 1 (MLL1) and tissue inhibitors of metalloproteinase 3 (TIMP3) [ 72 ] Dual-luciferase report assay and investigation of both cell lines and samples of patients with acute lymphoblastic leukemia confirmed that miR-137 directly targets lysine-specific demethylase JARID1B mRNA, leading to abnormal levels of H3K4me3 and H3K4me2 [ 86 ].…”

Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review

“…Fu et al ( Fu et al, 2017 ) reported that overexpression of miR-21 could inhibit granulosa cells apoptosis by inhibiting the expression of PDCD4. Tissue inhibitor of metalloproteinase-3 (TIMP3) has been reported to suppress the metastasis of glioma cells and breast cancer cells ( Hu et al, 2021 ; Wei et al, 2021 ). MMP2 is a downstream gene of TIMP3 and affects keratinocyte migration by degrading the extracellular matrix ( Caley et al, 2015 ; Lazaro et al, 2016 ).…”

Tissue Inhibitor of Metalloproteases 3 (TIMP-3): In Vivo Analysis Underpins Its Role as a Master Regulator of Ectodomain Shedding

“…Long non-coding RNAs (lncRNAs) are a new class of epigenetic regulators that play important roles in several diseases, including cancer. Long non-coding RNA reprogramming (lncRNA-ROR) was shown to recruit the transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription [24].…”