|Title:||Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells||Authors:||Cheng Y.-C
|Keywords:||breast cancer; function; hypoxia; long noncoding RNA; microRNA; mitochondria||Issue Date:||2021||Journal Volume:||11||Source:||Frontiers in Oncology||Abstract:||
Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression. ? Copyright ? 2021 Cheng, Su, Chen, Lu, Chuang, Tsai, Chuang and Lai.
|ISSN:||2234943X||DOI:||10.3389/fonc.2021.663114||metadata.dc.subject.other:||c terminal Src kinase; cyclic AMP responsive element binding protein; formin binding protein 1; hypoxia inducible factor 1alpha; hypoxia inducible factor 2alpha; long untranslated RNA; microRNA; microRNA 1293; microRNA 1297; microRNA 200b; microRNA 26a; microRNA 26a 5p; microRNA 26b 5p; microRNA 338 5p; mitochondrial oxygen responsive transcript 1; phosphoinositide 3 kinase regulatory subunit 2; protein phosphatase 1 regulatory inhibitor subunit 14B; protein phosphatase 1 regulatory subunit 3C; Ras protein; small interfering RNA; unclassified drug; Article; bacterium isolation; bioinformatics; breast cancer; cancer growth; cell migration; cell migration assay; cell proliferation; chromatin immunoprecipitation; colony formation; controlled study; disease exacerbation; down regulation; enzyme linked immunosorbent assay; gene expression profiling; gene knockdown; gene overexpression; genetic transfection; hypoxia; immunoprecipitation; luciferase assay; MCF-7 cell line; microarray analysis; mitochondrial respiration; protein expression; protein function; real time polymerase chain reaction; reoxygenation; RNA extraction; RNA interference; transcription initiation; tumor suppressor gene; ubiquitination; upregulation; Western blotting
|Appears in Collections:||分子與細胞生物學研究所|
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