Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleExperimental Studies

Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells

MADOKA NAEMURA, CHIHIRO MURASAKI, YASUTOSHI INOUE, HARUNA OKAMOTO and YOJIRO KOTAKE
Anticancer Research October 2015, 35 (10) 5377-5382;
MADOKA NAEMURA
Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHIHIRO MURASAKI
Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YASUTOSHI INOUE
Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HARUNA OKAMOTO
Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YOJIRO KOTAKE
Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, Fukuoka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ykotake@fuk.kindai.ac.jp
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background: Long noncoding RNA ANRIL (antisense non-coding RNA in the INK4 locus) represses p15 and p16, which induce cell-cycle arrest at G1 phase, leading to enhanced cell proliferation of normal fibroblasts. Herein we report that ANRIL is also involved in the regulation of cancer-cell proliferation. Materials and Methods: HeLa and H1299 cells were transfected with ANRIL siRNAs. At 72 h post-transfection, cells were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell-cycle analysis. Results: qRT-PCR showed that ANRIL is highly expressed in these cancer cells compared to normal fibroblasts. Depletion of ANRIL increased p15 expression, with no impact on p16 or ARF (alternative reading frame) expression, and caused cell-cycle arrest at the G2/M phase, leading to inhibition of proliferation of H1299 and HeLa cells. Conclusion: ANRIL positively regulates the proliferation of cancer cells, such as H1299 and HeLa cells, via regulating p15 and other genes related to G2/M phase control.

  • Long noncoding RNA
  • ANRIL
  • p15
  • p16
  • cell cycle

Antisense non-coding RNA in the INK4 (inhibitors of cyclin dependent kinase 4) locus (ANRIL) is a long noncoding RNA (lncRNA) located in the human chromosome 9p21 region. The INK4 locus encodes three tumor-suppressor genes: CDK (cyclin dependent kinase) inhibitors (CKIs) p15 and p16, and ARF (alternative reading frame), which is a positive regulator of p53. This region is frequently mutated or its expression silenced in human cancer (1-4). CKIs bind to and inhibit the activity of specific cyclin–CDK complexes, preventing G1 to S transition of the cell-cycle (5, 6). Among these CKIs, p15 and p16 are induced by a variety of oncogenes, such as activating RAS (rat sarcoma) mutants, causing stable cell-cycle arrest through inhibiting cyclin D-dependent CDK4/6 activity (7-9). ARF is also induced by various oncogenes, such as c-MYC (cellular myelocytomatosis oncogene), and antagonizes the activity of MDM2 (transformed mouse 3T3 cell double minute 2) ubiquitin ligase, thereby stabilizing p53 tumour suppressor protein and causing cell-cycle arrest (10-13). The activation of the INK4 locus is therefore important to protect cells from hyper-proliferative stimulation induced by oncogenic insults.

The ANRIL promoter is located between p15 and ARF, and ANRIL is transcribed in the antisense direction with these genes (14). Yap et al. (15) and our group (16) reported that ANRIL is involved in the transcriptional repression of the INK4 locus (15, 16). Inhibition of ANRIL in human normal fibroblasts increases the expression of p15 and p16, leading to a decrease in cell proliferation. Yap et al. showed that ANRIL associates with CBX7 (chromobox 7), a component of polycomb repression complex (PRC)-1 (15). We also showed that ANRIL associates with SUZ12 (suppressor of zeste 12 homolog), a component of PRC-2 (16). Inhibition of ANRIL disrupts the binding of PRC-1 and -2 on the INK4 locus, indicating that ANRIL recruits PRC-1 and -2 on the INK4 locus, leading to the repression of p15 and p16 transcription (15, 16). ANRIL is also involved in the occupancy of PRC-1 and -2 on other genes located on different chromosomes, indicating that it functions on different chromosomes to regulate target genes in trans (17). The trans-regulation by ANRIL is dependent on its Alu motif (17). Several studies showed that depletion or overexpression of ANRIL causes changes in the expression levels of many genes involved in cell proliferation, cell adhesion, gene expression, and apoptosis, suggesting that ANRIL is involved in multiple cellular functions (17-19). In the present study, we investigated the role of ANRIL in the proliferation of cancer cells, namely human non-small cell lung cancer H1299 cells and HeLa cervical cancer cells.

Materials and Methods

Cell culture. All cell lines used in this study were cultured in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Carlsbad, CA, USA) containing 10% foetal bovine serum (GIBCO, Grand Island, NY, USA) and incubated at 37°C in an atmosphere containing 5% CO2.

RNA interference. siRNA oligonucleotides against ANRIL (SIGMA-ALDRICH, Tokyo, Japan) were transfected into HeLa and H1299 cells using Lipofectamine RNAiMAX (Invitrogen), according to the manufacturer's instructions. HeLa and H1299 cells were incubated 72 h after transfection before analyses. The nucleotide sequence of ANRIL siRNA was 5’-GGUCAUCUCAUUGCUCUAU-3’ with 3’ dTdT overlaps.

Reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR). Total RNA was isolated by the RNeasy Plus kit (Qiagen, Tokyo, Japan) according to the manufacturer's instructions. The isolated total RNA was reversed transcribed into cDNA using SuperScript Reverse Transcriptase II (Invitrogen). For qualitative PCR, the produced cDNA was amplified by the specific primer sets: ANRIL, 5’-TGCTCTATCCGCC AATCAGG-3’ and 5’-GGGCCTCAGTGGCACATACC-3’; glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 5’-GCAAATTCCATGGCACCGT-3’ and 5’-TCGCCCCACTTGATT TTGG-3’; ribosomal protein L32 (RPL32), 5’-GGCGGAAACCCAGAGGCATTGA-3’ and 5’-CCTGGCATTGGGGTTGGTGACTCT-3’. For qRT-PCR, the produced cDNA was added to SYBR Green PCR master mix (Qiagen) and amplify by the specific primer sets: p16, 5’-CGGTCGGAGGCCGATCCAG-3’ and 5’-GCGCCGTGGAGCAGCAGCAGCT-3’; p15, 5’-AAGCTGAGCCCAGGTCTCCTA-3’ and 5’-CCACCGTTGGCCGTAAACT-3’; ARF, 5’-CCCTCGTGCTGATGCTACTG-3’ and 5’-ACCTGGTCTTCTAGGAAGCGG-3’; GAPDH, 5’-GCAAATTCCATGGCAC CGT-3’ and 5’-TCGCCCCACTTGATTTTGG-3’. Assays were performed in triplicate on a Mx3000P Real-Time Q-PCR System (Agilent Technologies, Santa Clara, CA, USA).

Cell-cycle analysis. HeLa cells were fixed overnight in 70% ethanol at −20°C. The DNA of fixed cells was stained by Muse™ Cell Cycle Kit (Merck Millipore, Darmstadt, Germany) according to the manufacturer's instructions. Cells were analyzed by Muse™ Cell Analyzer and analysis software (Merck Millipore).

Results

We first examined the expression of ANRIL in various human cell lines. RT-PCR assay showed that ANRIL was highly expressed in several cancer cell types, including ABC-1, H1299 (human non-small cell lung cancer), HeLa (cervical cancer) and Saos-2 cells (osteosarcoma) compared with WI38 and TIG-3 cells (normal diploid foetal lung fibroblasts) (Figure 1).

We previously reported that ANRIL positively regulates the proliferation of human normal diploid foetal lung fibroblasts (16). Therefore, we next determined whether ANRIL is also involved in the regulation of cancer-cell proliferation. We knocked-down ANRIL using specific siRNA oligonucleotides in cancer cells with high expression of ANRIL, namely HeLa and H1299 cells. RT-PCR assay confirmed that these siRNAs reduced ANRIL expression to nearly undetectable levels in HeLa cells (Figure 2A). The depletion of ANRIL resulted in repression of HeLa cell proliferation (Figure 2B and C). In H1299 cells with knocked-down ANRIL, we also observed a substantial decrease of H1299 cell proliferation (Figure 2D-F). These results suggest that ANRIL positively regulates the proliferation of HeLa and H1299 cells.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Expression levels of ANRIL (antisense non-coding RNA in the INK4 locus) in various human cells. The levels of ANRIL expression were determined by RT-PCR. RPL32 (ribosomal protein L32) was used as an internal control.

Yap et al. (15) and our group (16) previously reported that ANRIL is involved in the repression of p15 and p16 transcription. We, therefore, examined the effect of ANRIL silencing on the expression of genes of the INK4 locus including p15, p16, and ARF in HeLa and H1299 cells. qRT-PCR showed that silencing ANRIL in HeLa cells resulted in an about two-fold increase in p15 mRNA, with no changes in p16 or ARF mRNA levels (Figure 3A). Silencing ANRIL in H1299 cells also resulted in a more than fourfold increase in p15 mRNA, but no changes were observed for ARF mRNA (p16 was not detected) (Figure 3B). These results suggest that ANRIL is involved in p15 repression in cancer cells, such as HeLa and H1299 cells.

Given that silencing ANRIL increases the mRNA level of p15, which causes G1 phase arrest, we next examined the effect of silencing ANRIL on the cell cycle using Muse™Cell Analyzer. Contrary to our expectation, silencing of ANRIL in HeLa cells induced a pronounced G2/M phase accumulation compared with control cells (Figure 4A and B), suggesting that ANRIL regulates the G2/M phase of the cell cycle in HeLa cells.

Discussion

Recent studies revealed that several lncRNAs have pivotal roles in critical cellular processes, including proliferation, differentiation, apoptosis, and senescence (20-23). ANRIL is involved in the regulation of cellular senescence of normal human diploid foetal lung fibroblasts through the regulation of p15 and p16 transcription (15, 16). In this study, we showed that ANRIL is also involved in the regulation of proliferation of cancer cells, such as the human H1299 non-small cell lung cancer cells and HeLa cervical cancer cells. Silencing ANRIL increased p15 expression, but not p16 and ARF, suggesting that ANRIL represses mainly p15 transcription in these cancer cells. p15 inhibits the activity of cyclin D–CDK4/6, causing cell-cycle arrest at the G1 phase. Interestingly, silencing ANRIL caused cell-cycle arrest at G2/M phase in these cancer cells, not G1 phase. Recent reports demonstrated that ANRIL recruits PRC-1 and -2 to target genes located on different chromosomes to regulate gene expression (17). In support of this notion, silencing ANRIL impacts the expression of a large number of genes (18, 19). Thus, ANRIL may be involved in the regulation of genes that control G2/M phase in a trans-acting manner.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Silencing of ANRIL (antisense non-coding RNA in the INK4 locus) represses the proliferation of HeLa and H1299 cells. A: HeLa cells were transfected with control (Ctr-i) or ANRIL siRNA oligonucleotides. At 72 h after transfection, cells were harvested and subjected to RT-PCR (reverse transcription-polymerase chain reaction) to determine the level of ANRIL. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was used as an internal control. B: HeLa cells transfected with control or ANRIL siRNA oligonucleotides were observed by phase-contrast microscopy at 72 h after transfection. C: After initial seeding of 5×105 cells, HeLa cells were incubated overnight, and then transfected with control or ANRIL siRNA oligonucleotides. At 72 h after transfection, viable HeLa cells were counted by Trypan Blue staining. D: H1299 cells were transfected with control (Ctr) or ANRIL siRNA oligonucleotides. At 72 h after transfection, cells were harvested and subjected to RT-PCR as in (A). E: H1299 cells transfected with control or ANRIL siRNA oligonucleotides were observed as in (B). F: After initial seeding of 1×105 cells, H1299 cells were incubated overnight, and then transfected with control or ANRIL siRNA oligonucleotides. Viable H1299 cells were counted as in (C).

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Silencing of ANRIL (antisense non-coding RNA in the INK4 locus) increases p15 mRNA expression. A: HeLa cells were transfected with control (Ctr-i) or ANRIL siRNA oligonucleotides. At 72 h after transfection, cells were harvested. The effects of ANRIL silencing on the expression of p15, p16 and ARF (alternative reading frame) were determined by qRT-PCR. The results are expressed relative to the corresponding values for control cells. The mean values and standard deviations were calculated from the data of three independent experiments. B: The effects of ANRIL silencing on the expression of p15 and ARF in H1299 cells were determined by qRT-PCR as in (A).

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

Silencing of ANRIL (antisense non-coding RNA in the INK4 locus) causes cell-cycle arrest at the G2/M phase. A: HeLa cells transfected with control (Ctr-i) or ANRIL siRNA oligonucleotides were analyzed by Muse™ Cell Analyzer at 72 h after transfection. B: The percentage of total cells present in the G0/G1, S and G2/M phases of the cell cycle are shown.

We also showed that ANRIL is highly expressed in different types of human cancer cell, such as non-small cell lung cancer (ABC-1 and H1299), cervical cancer (HeLa) and osteosarcoma (Saos-2). High levels of ANRIL have been previously observed in human cancer, including prostate (16) and gastric (24). The molecular mechanism underlying aberrant expression of ANRIL in cancer remains to be elucidated. It was reported that transcription factor E2F1 induced by ATM (ataxia telangiectasia mutated) binds to the ANRIL promoter and activates its transcription in response to DNA damage (18, 25). Increased expression of E2F1 has been observed in many types of human cancer (26), suggesting that deregulation of E2F1 might lead to aberrant expression of ANRIL in cancer.

p15 and p16 are activated by oncogenes, including an oncogenic form of small GTPase RAS (called oncogenic RAS), causing stable cell-cycle arrest in order to protect cells from hyper-proliferation (7-9). Recently, we reported that oncogenic RAS reduces the expression of ANRIL (15, 27). The decrease of ANRIL by oncogenic RAS might be required for p15- and p16-dependent cell-cycle arrest. We, therefore, postulate that aberrant expression of ANRIL might disrupt protection by p15 and p16, leading to oncogenic transformation.

Acknowledgements

The Authors thank the members of the Kotake Laboratory for their technical assistance and helpful discussions. This work was supported by JSPS KAKENHI grant number 26430127 (to YK) and the Takeda Science Foundation (to YK).

  • Received May 8, 2015.
  • Revision received June 29, 2015.
  • Accepted July 1, 2015.
  • Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved

References

  1. ↵
    1. Ruas M,
    2. Peters G
    : The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1378: F115-177, 1998.
    OpenUrlPubMed
    1. Sharpless NE
    : INK4a/ARF: a multifunctional tumor-suppressor locus. Mutat Res 576: 22-38, 2005.
    OpenUrlCrossRefPubMed
    1. Aravidis C,
    2. Panani AD,
    3. Kosmaidou Z,
    4. Thomakos N,
    5. Rodolakis A,
    6. Antsaklis A
    : Detection of numerical abnormalities of chromosome 9 and p16/CDKN2A gene alterations in ovarian cancer with FISH analysis. Anticancer Res 32: 5309-5313, 2012.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Boukhari A,
    2. Alhosin M,
    3. Bronner C,
    4. Sagini K,
    5. Truchot C,
    6. Sick E,
    7. Schini-Kerth VB,
    8. Andre P,
    9. Mely Y,
    10. Mousli M,
    11. Gies JP
    : CD47 Activation-induced UHRF1 overexpression is associated with silencing of tumor-suppressor gene p16INK4A in glioblastoma cells. Anticancer Res 35: 149-157, 2015.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Pei XH,
    2. Xiong Y
    : Biochemical and cellular mechanisms of mammalian CDK inhibitors: a few unresolved issues. Oncogene 24: 2787-2795, 2005.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Sherr CJ,
    2. Roberts JM
    : CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13: 1501-1512, 1999.
    OpenUrlFREE Full Text
  5. ↵
    1. Braig M,
    2. Lee S,
    3. Loddenkemper C,
    4. Rudolph C,
    5. Peters AH,
    6. Schlegelberger B,
    7. Stein H,
    8. Dorken B,
    9. Jenuwein T,
    10. Schmitt CA
    : Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436: 660-665, 2005.
    OpenUrlCrossRefPubMed
    1. Brookes S,
    2. Rowe J,
    3. Ruas M,
    4. Llanos S,
    5. Clark PA,
    6. Lomax M,
    7. James MC,
    8. Vatcheva R,
    9. Bates S,
    10. Vousden KH,
    11. Parry D,
    12. Gruis N,
    13. Smit N,
    14. Bergman W,
    15. Peters G
    : INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J 21: 2936-2945, 2002.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Serrano M,
    2. Lin AW,
    3. McCurrach ME,
    4. Beach D,
    5. Lowe SW
    : Oncogenic RAS provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593-602, 1997.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Kim WY,
    2. Sharpless NE
    : The regulation of INK4/ARF in cancer and aging. Cell 127: 265-275, 2006.
    OpenUrlCrossRefPubMed
    1. Pomerantz J,
    2. Schreiber-Agus N,
    3. Liegeois NJ,
    4. Silverman A,
    5. Alland L,
    6. Chin L,
    7. Potes J,
    8. Chen K,
    9. Orlow I,
    10. Lee HW,
    11. Cordon-Cardo C,
    12. DePinho RA
    : The INK4A tumor-suppressor gene product, p19ARF, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92: 713-723, 1998.
    OpenUrlCrossRefPubMed
    1. Stott FJ,
    2. Bates S,
    3. James MC,
    4. McConnell BB,
    5. Starborg M,
    6. Brookes S,
    7. Palmero I,
    8. Ryan K,
    9. Hara E,
    10. Vousden KH,
    11. Peters G
    : The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. EMBO J 17: 5001-5014, 1998.
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Zhang Y,
    2. Xiong Y,
    3. Yarbrough WG
    : ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor-suppression pathways. Cell 92: 725-734, 1998.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Pasmant E,
    2. Laurendeau I,
    3. Heron D,
    4. Vidaud M,
    5. Vidaud D,
    6. Bieche I
    : Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression co-clusters with ARF. Cancer Res 67: 3963-3969, 2007.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Yap KL,
    2. Li S,
    3. Munoz-Cabello AM,
    4. Raguz S,
    5. Zeng L,
    6. Mujtaba S,
    7. Gil J,
    8. Walsh MJ,
    9. Zhou MM
    : Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38: 662-674, 2010.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Kotake Y,
    2. Nakagawa T,
    3. Kitagawa K,
    4. Suzuki S,
    5. Liu N,
    6. Kitagawa M,
    7. Xiong Y
    : Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor-suppressor gene. Oncogene 30: 1956-1962, 2011.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Holdt LM,
    2. Hoffmann S,
    3. Sass K,
    4. Langenberger D,
    5. Scholz M,
    6. Krohn K,
    7. Finstermeier K,
    8. Stahringer A,
    9. Wilfert W,
    10. Beutner F,
    11. Gielen S,
    12. Schuler G,
    13. Gabel G,
    14. Bergert H,
    15. Bechmann I,
    16. Stadler PF,
    17. Thiery J,
    18. Teupser D
    : Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet 9: e1003588, 2013.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Sato K,
    2. Nakagawa H,
    3. Tajima A,
    4. Yoshida K,
    5. Inoue I
    : ANRIL is implicated in the regulation of nucleus and potential transcriptional target of E2F1. Oncol Rep 24: 701-707, 2010.
    OpenUrlPubMed
  14. ↵
    1. Congrains A,
    2. Kamide K,
    3. Katsuya T,
    4. Yasuda O,
    5. Oguro R,
    6. Yamamoto K,
    7. Ohishi M,
    8. Rakugi H
    : CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun 419: 612-616, 2012.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Batista PJ,
    2. Chang HY
    : Long non-coding RNAs: cellular address codes in development and disease. Cell 152: 1298-1307, 2013.
    OpenUrlCrossRefPubMed
    1. Fatica A,
    2. Bozzoni I
    : Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15: 7-21, 2014.
    OpenUrlCrossRefPubMed
    1. Kitagawa M,
    2. Kotake Y,
    3. Ohhata T
    : Long non-coding RNAs involved in cancer development and cell fate determination. Curr Drug Targets 13: 1616-1621, 2012.
    OpenUrlPubMed
  16. ↵
    1. Kitagawa M,
    2. Kitagawa K,
    3. Kotake Y,
    4. Niida H,
    5. Ohhata T
    : Cell-cycle regulation by long non-coding RNAs. Cell Mol Life Sci 70: 4785-4794, 2013.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Zhang EB,
    2. Kong R,
    3. Yin DD,
    4. You LH,
    5. Sun M,
    6. Han L,
    7. Xu TP,
    8. Xia R,
    9. Yang JS,
    10. De W,
    11. Chen J
    : Long non-coding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget 5: 2276-2292, 2014.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Wan G,
    2. Mathur R,
    3. Hu X,
    4. Liu Y,
    5. Zhang X,
    6. Peng G,
    7. Lu X
    : Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal 25: 1086-1095, 2013.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Chen HZ,
    2. Tsai SY,
    3. Leone G
    : Emerging roles of E2Fs in cancer: an exit from cell-cycle control. Nat Rev Cancer 9: 785-797, 2009.
    OpenUrlCrossRefPubMed
  20. ↵
    1. Kotake Y,
    2. Naemura M,
    3. Kitagawa K,
    4. Niida H,
    5. Tsunoda T,
    6. Shirasawa S,
    7. Kitagawa M
    : Oncogenic Ras influences the expression of multiple lncRNAs. Cytotechnology, 2015, in press.
PreviousNext
Back to top

In this issue

Anticancer Research: 35 (10)
Anticancer Research
Vol. 35, Issue 10
October 2015
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
1 + 1 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells
MADOKA NAEMURA, CHIHIRO MURASAKI, YASUTOSHI INOUE, HARUNA OKAMOTO, YOJIRO KOTAKE
Anticancer Research Oct 2015, 35 (10) 5377-5382;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Long Noncoding RNA ANRIL Regulates Proliferation of Non-small Cell Lung Cancer and Cervical Cancer Cells
MADOKA NAEMURA, CHIHIRO MURASAKI, YASUTOSHI INOUE, HARUNA OKAMOTO, YOJIRO KOTAKE
Anticancer Research Oct 2015, 35 (10) 5377-5382;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgements
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • OIP5-AS1 Promotes Proliferation of Non-small-cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Cells
  • Long Noncoding RNA ANROC on the INK4 Locus Functions to Suppress Cell Proliferation
  • Long Noncoding RNA, ANRIL, Regulates the Proliferation of Head and Neck Squamous Cell Carcinoma
  • The Long Noncoding RNA OIP5-AS1 Is Involved in the Regulation of Cell Proliferation
  • Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells
  • Long Non-coding RNA, PANDA, Contributes to the Stabilization of p53 Tumor Suppressor Protein
  • Google Scholar

More in this TOC Section

  • Docosahexaenoic Acid Potentiates the Anticancer Effect of the Menadione/Ascorbate Redox Couple by Increasing Mitochondrial Superoxide and Accelerating ATP Depletion
  • Streptonigrin Mitigates Lung Cancer-induced Cachexia by Suppressing TCF4/TWIST1-induced PTHLH Expression
  • Atezolizumab Retains Cellular Binding to Programmed Death Ligand 1 Following Aerosolization via Mesh Nebulizer
Show more Experimental Studies

Similar Articles

Keywords

  • long noncoding RNA
  • ANRIL
  • p15
  • p16
  • cell cycle
Anticancer Research

© 2023 Anticancer Research

Powered by HighWire