Dataset Information

LINC00355 regulates p27^KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

ABSTRACT: Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27^Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.

SUBMITTER: Eteleeb AM

PROVIDER: S-EPMC9007952 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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LINC00355 regulates p27<sup>KIP</sup> expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Eteleeb Abdallah M AM Thunuguntla Prasanth K PK Gelev Kyla Z KZ Tang Cynthia Y CY Rozycki Emily B EB Miller Alexander A Lei Jonathan T JT Jayasinghe Reyka G RG Dang Ha X HX White Nicole M NM Reis-Filho Jorge S JS Mardis Elaine R ER Ellis Matthew J MJ Ding Li L Silva-Fisher Jessica M JM Maher Christopher A CA

NPJ breast cancer 20220413 1

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355 ...[more]

PMID: 35418131

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Project description:Frequently referred to as the 'magic methyl effect', the installation of methyl groups-especially adjacent (α) to heteroatoms-has been shown to dramatically increase the potency of biologically active molecules1-3. However, existing methylation methods show limited scope and have not been demonstrated in complex settings1. Here we report a regioselective and chemoselective oxidative C(sp3)-H methylation method that is compatible with late-stage functionalization of drug scaffolds and natural products. This combines a highly site-selective and chemoselective C-H hydroxylation with a mild, functional-group-tolerant methylation. Using a small-molecule manganese catalyst, Mn(CF3PDP), at low loading (at a substrate/catalyst ratio of 200) affords targeted C-H hydroxylation on heterocyclic cores, while preserving electron-neutral and electron-rich aryls. Fluorine- or Lewis-acid-assisted formation of reactive iminium or oxonium intermediates enables the use of a mildly nucleophilic organoaluminium methylating reagent that preserves other electrophilic functionalities on the substrate. We show this late-stage C(sp3)-H methylation on 41 substrates housing 16 different medicinally important cores that include electron-rich aryls, heterocycles, carbonyls and amines. Eighteen pharmacologically relevant molecules with competing sites-including drugs (for example, tedizolid) and natural products-are methylated site-selectively at the most electron rich, least sterically hindered position. We demonstrate the syntheses of two magic methyl substrates-an inverse agonist for the nuclear receptor RORc and an antagonist of the sphingosine-1-phosphate receptor-1-via late-stage methylation from the drug or its advanced precursor. We also show a remote methylation of the B-ring carbocycle of an abiraterone analogue. The ability to methylate such complex molecules at late stages will reduce synthetic effort and thereby expedite broader exploration of the magic methyl effect in pursuit of new small-molecule therapeutics and chemical probes.

Dataset Information

LINC00355 regulates p27^KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Publications

LINC00355 regulates p27<sup>KIP</sup> expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

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Dataset Information

LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Publications

LINC00355 regulates p27<sup>KIP</sup> expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

LINC00355 regulates p27^KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.