lincRNA-RoR and miR-145 Regulate Invasion in Triple-Negative Breast Cancer via Targeting ARF6

Eades, Gabriel; Wolfson, Benjamin; Zhang, Yongshu; Li, Qinglin; Yao, Yuan; Zhou, Qun

doi:10.1158/1541-7786.mcr-14-0251

Cited by 225 publications

(235 citation statements)

References 33 publications

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“…In this, it could be analogous to other ncRNAs, such as Linc-ROR, LncRNA-ATB, and MALAT1, which stabilize mRNAs by acting as competing endogenous RNAs to sequester miRNAs and inhibit the miRNA-mediated decay of their target mRNAs. [34][35][36] Alternatively, BC200 RNA may increase the stability of S100A11 mRNA by interacting with complementary sequences. There is a putative BC200 RNA binding site between positions ¡30 and ¡15 of S100A11 mRNA relative to the start codon (C 1 would be A of the ATG codon).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

et al. 2017

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Although BC200 RNA is best known as a neuron-specific non-coding RNA, it is overexpressed in various cancer cells. BC200 RNA was recently shown to contribute to metastasis in several cancer cell lines, but the underlying mechanism was not understood in detail. To examine this mechanism, we knocked down BC200 RNA in cancer cells, which overexpress the RNA, and examined cell motility, profiling of ribosome footprints, and the correlation between cell motility changes and genes exhibiting altered ribosome profiles. We found that BC200 RNA knockdown reduced cell migration and invasion, suggesting that BC200 RNA promotes cell motility. Our ribosome profiling analysis identified 29 genes whose ribosomal occupations were altered more than 2-fold by BC200 RNA knockdown. Many (> 30%) of them were directly or indirectly related to cancer progression. Among them, we focused on S100A11 (which showed a reduced ribosome footprint) because its expression was previously shown to increase cellular motility. S100A11 was decreased at both the mRNA and protein levels following knockdown of BC200 RNA. An actinomycin-chase experiment showed that BC200 RNA knockdown significantly decreased the stability of the S100A11 mRNA without changing its transcription rate, suggesting that the downregulation of S100A11 was mainly caused by destabilization of its mRNA. Finally, we showed that the BC200 RNAknockdown-induced decrease in cell motility was mainly mediated by S100A11. Together, our results show that BC200 RNA promotes cell motility by stabilizing S100A11 transcripts.

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Section: Discussionmentioning

confidence: 99%

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

et al. 2017

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“…18 LncRNA ROR may be used to enhance the invasive ability of female breast cancer by inhibiting the expression of miR-145. 19 Also, lncRNAs screening is beneficial in the diagnosis, sub-classification, and the personalized treatment of NSCLC. 20 Besides this, the PI3K/Akt/mTOR pathway may be activated in NSCLC, and LncRNA ROR has been proven to suppress angiogenesis via the PI3K/Akt/mTOR signaling pathway in human gliomas.…”

Section: Introductionmentioning

confidence: 99%

Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway

Shi

Zhou

et al. 2017

Tumour Biol.

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This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colonyforming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumorformation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.

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“…lncRNA-RoR acts as a competitive sponge for miR-145, increasing expression of other miR-145 targets. This is a mechanism for maintaining self-renewal signaling in human embryonic stem cells, triple-negative breast cancer, and endometrial tumor spheres (25)(26)(27). miRNAs can also regulate lncRNAs by targeting them for degradation via the RNA-induced silencing complex (28).…”

mentioning

confidence: 99%

MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis

Gernapudi

Wolfson

Zhang

et al. 2016

Molecular and Cellular Biology

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113

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More than 40% of the U.S. population are clinically obese and suffer from metabolic syndrome with an increased risk of postmenopausal estrogen receptor-positive breast cancer. Adipocytes are the primary component of adipose tissue and are formed through adipogenesis from precursor mesenchymal stem cells. While the major molecular pathways of adipogenesis are understood, little is known about the noncoding RNA signaling networks involved in adipogenesis. Using adipocyte-derived stem cells (ADSCs) isolated from wild-type and microRNA 140 (miR-140) knockout mice, we identify a novel miR-140/long noncoding RNA (lncRNA) NEAT1 signaling network necessary for adipogenesis. miR-140 knockout ADSCs have dramatically decreased adipogenic capabilities associated with downregulation of NEAT1 expression. We identified a miR-140 binding site in NEAT1 and found that mature miR-140 in the nucleus can physically interact with NEAT1, leading to increased NEAT1 expression. We demonstrated that reexpression of NEAT1 in miR-140 knockout ADSCs is sufficient to restore their ability to undergo differentiation. Our results reveal an exciting new noncoding RNA signaling network that regulates adipogenesis and that is a potential new target in the prevention or treatment of obesity. More than 40% of American adults are overweight or obese, and there are over 40 million obese women in America (1). Obese and overweight women are at greater risk for postmenopausal breast cancer and have dramatically higher rates of cancer recurrence and mortality (2, 3). Obesity is characterized by metabolic imbalance leading to adipocyte hypertrophy and hyperplasia and the excess accumulation of adipose tissue. During adipogenesis, mesenchymal stem cells (MSC) commit to the adipogenic lineage, forming proliferative, MSC-like cells called preadipocytes. By differentiating into mature adipocytes, preadipocytes replenish the nonproliferative mature adipocytes that are the bulk of white adipose tissue (4). Mature adipocytes secrete hormones and adipokines that, in addition to their metabolic function, promote breast tumor aggressiveness and invasion (5). Deciphering the mechanisms of preadipocyte differentiation and adipocyte-breast cancer cell interaction will greatly further our understanding of and our ability to treat breast cancers.MicroRNAs (miRNAs) are essential regulators of cellular function and gene expression. After nuclear processing, miRNA precursors are exported to the cytoplasm, where the mature miRNA is formed. miRNAs associate with the RNA-induced silencing complex (RISC) and base pair to seed sequences in the 3= untranslated region (UTR) of target mRNAs. This guides the RISC to the mRNA, causing degradation or inhibition of translation. miRNAs primarily function in the cytoplasm; however, some have been shown to translocate back into the nucleus and degrade nuclear RNA molecules (6). Nuclear miRNAs have also been shown to mediate mRNA upregulation by RNA activation (RNAa).

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lincRNA-RoR and miR-145 Regulate Invasion in Triple-Negative Breast Cancer via Targeting ARF6

Cited by 225 publications

References 33 publications

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway

MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis

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