Skip to main content

Advertisement

Springer Nature Link
Log in

LncRNA-SNHG16 promotes proliferation and migration of acute myeloid leukemia cells via PTEN/PI3K/AKT axis through suppressing CELF2 protein

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

The silence of lncRNA small nucleolar RNA host gene 16 (SNHG16) suppressed acute lymphoblastic leukemia (ALL) cell proliferation and migration, whereas its role in acute myeloid leukemia (AML) still lacks clarity. This study showed that SNHG16 was upregulated in AML patients and cells. And SNHG16 overexpression remarkably enhanced the proliferation and migration capacities of HL60 and AML-193 cells, while SNHG16 knockdown acted the opposite way. Subsequently, we revealed that SNHG16 directly bound to CELF2 (CUGBP Elav-like family member 2) protein, and caused CELF2 mRNA unstably and proteins reducing. CELF2 was decreased both in AML patients and cells. CELF2 overexpression or interference weakened the effect of overexpressing or silencing SNHG16 on proliferation and migration. Moreover, the transfection of pcDNA-CELF2 elevated PTEN (phosphatase and tensin homolog) activity and hindered the phosphoinositide 3-kinase (PI3K)/AKT signaling. And SNHG16 reduced PTEN activity and promoted the PI3K/AKT pathway activation by restraining CELF2. Furthermore, GDC-0941 (a specific inhibitor of the PI3K/AKT pathway) impeded the effect of SNHG16 increase, and bpV(pic) (a specific PTEN inhibitor) declined the effect of SNHG16 decrease on cell proliferation and migration. Taken together, the present study indicated that SNHG16 promoted proliferation and migration of AML cells via PTEN/PI3K/AKT axis through suppressing CELF2 protein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Ajith S, Gazzara MR, Cole BS, Shankarling G, Martinez NM et al. 2016 Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells. RNA Biol. 13 569–581

    Article  Google Scholar 

  • Ayala YM, De Conti L, Avendaño-Vázquez SE, Dhir A, Romano M et al. 2011 TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 30 277–288

    Article  CAS  Google Scholar 

  • Bao X, Zhang L and Song W 2019 LncRNA SNHG1 overexpression regulates the proliferation of acute myeloid leukemia cells through miR-488-5p/NUP205 axis. Eur. Rev. Med. Pharmacol. Sci. 23 5896–5903

    PubMed  Google Scholar 

  • Blech-Hermoni Y, Stillwagon S and Ladd A 2013 Diversity and conservation of CELF1 and CELF2 RNA and protein expression patterns during embryonic development. Dev. Dynam. 242 767–777

    Article  CAS  Google Scholar 

  • De Kouchkovsky I and Abdul-Hay M 2016 Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 6 e441–e441

    Article  Google Scholar 

  • Du Z, Fei T, Verhaak RG, Su Z, Zhang Y et al. 2013 Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat. Struct. Mol. Biol. 20 908

    Article  CAS  Google Scholar 

  • Fan B, Jiao BH, Fan FS, Lu SK, Song J et al. 2015 Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2. Int. J. Oncol. 47 1025–1033

    Article  CAS  Google Scholar 

  • Feng F, Chen AP, Huang JJ, Xia QH, Chen YG et al. 2018 Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/β‐catenin pathway axis. J. Cell. Biochem. 119 9408–9418

    Article  CAS  Google Scholar 

  • Gao TY, Liu XX, He BS, Pan YQ and Wang SK 2020 Long non-coding RNA 91H regulates IGF2 expression by interacting with IGF2BP2 and promotes tumorigenesis in colorectal cancer. Artif. Cell. Nanomed. B. 48 664–671

    Article  CAS  Google Scholar 

  • Han W, Du XM, Liu M, Wang J, Sun LX et al. 2019 Increased expression of long non-coding RNA SNHG16 correlates with tumor progression and poor prognosis in non-small cell lung cancer. Int. J. Biol. Macromol. 121 270–278

    Article  CAS  Google Scholar 

  • Hornstein E, Harel H, Levy G and Meyuhas O 1999 Overexpression of poly (A)-binding protein down-regulates the translation or the abundance of its own mRNA. FEBS lett. 457 209–213

    Article  CAS  Google Scholar 

  • Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T et al. 2015 Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat. Genet. 47 1304

    Article  CAS  Google Scholar 

  • Kim J, Abdelmohsen K, Yang X, De S, Grammatikakis I et al. 2016 LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR. Nucleic Acids Res. 44 2378–2392

    Article  CAS  Google Scholar 

  • Li SF, Zhang SK and Chen J 2019 c-Myc induced upregulation of long non-coding RNA SNHG16 enhances progression and carcinogenesis in oral squamous cell carcinoma. Cancer Gene Ther. 26 400–410

    Article  Google Scholar 

  • Liu Q, Hu YG, Zhang M, Yan YS, Yu HM et al. 2018 microRNA-451 protects neurons against ischemia/reperfusion injury-induced cell death by targeting CELF2. Neuropsych. Dis. Treat. 14 2773

    Article  CAS  Google Scholar 

  • Liu SY, Zhang W, Liu K and Liu YH 2019 LncRNA SNHG16 promotes tumor growth of pancreatic cancer by targeting miR-218-5p. Biomed. Pharmacother. 114 108862

    Article  CAS  Google Scholar 

  • Lu W, Yu J, Shi F, Zhang J, Huang R et al. 2019 The long non-coding RNA Snhg3 is essential for mouse embryonic stem cell self-renewal and pluripotency. Stem Cell Res Ther 10 157–168

    Article  CAS  Google Scholar 

  • Martelli A, Nyakern M, Tabellini G, Bortul R, Tazzari P et al. 2006 Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 20 911–928

    Article  CAS  Google Scholar 

  • Mukhopadhyay D, Houchen CW, Kennedy S, Dieckgraefe BK and Anant S 2003 Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2. Mol. Cell 11 113–126

    Article  CAS  Google Scholar 

  • Pan JQ, Zhang YQ, Wang JH, Xu P and Wang W 2017 lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia. Int. J. Mol. Med. 39 663–671

    Article  CAS  Google Scholar 

  • Salmena L, Carracedo A and Pandolfi PP 2008 Tenets of PTEN tumor suppression. Cell 133 403–414

    Article  CAS  Google Scholar 

  • Shen Y, Liu SS, Fan J, Jin YH, Tian BL et al. 2017 Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions. Embo. Rep. 18 536–548

    Article  CAS  Google Scholar 

  • Subramaniam D, Natarajan G, Ramalingam S, Ramachandran I, May R et al. 2008 Translation inhibition during cell cycle arrest and apoptosis: Mcl-1 is a novel target for RNA binding protein CUGBP2. Am. J. Physiol-Gastr. L. 294 G1025-G1032

    CAS  Google Scholar 

  • Tian YJ, Wang YH, Xiao AJ, Li PL, Guo J et al. 2019 Long noncoding RNA SBF2-AS1 act as a ceRNA to modulate cell proliferation via binding with miR-188-5p in acute myeloid leukemia. Artif. Cell. Nanomed. B. 47 1730–1737

    Article  CAS  Google Scholar 

  • Vivanco I and Sawyers CL 2002 The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nat. Rev. Cancer 2 489–501

    Article  CAS  Google Scholar 

  • Wang JZ, Liu L, Sun YC, Xue YM, Qu JK et al. 2018 miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer. Biomed. Pharmacother. 101 406–413

    Article  CAS  Google Scholar 

  • Wang XL, Hu KJ, Chao Y and Wang L 2019 LncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis. Biomed. Pharmacother. 114 108798

    Article  CAS  Google Scholar 

  • Wen Q, Zhao L, Wang TT, Lv NN, Cheng XJ et al. 2019 LncRNA SNHG16 drives proliferation and invasion of papillary thyroid cancer through modulation of miR-497. OncoTargets Ther. 12 699

    Article  CAS  Google Scholar 

  • Wu JC, Luo SZ, Liu T, Lu LG and Xu MY 2019 linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin. FASEB J. 33 2105–2115

    Article  CAS  Google Scholar 

  • Xing CY, Hu XQ, Xie FF, Yu ZJ, Li HY et al. 2015 Long non-coding RNA HOTAIR modulates c‐KIT expression through sponging miR-193a in acute myeloid leukemia. FEBS lett. 589 1981–1987

    Article  CAS  Google Scholar 

  • Yeung YT, Fan S, Lu B, Yin S, Yang S et al. 2019 CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction. Carcinogenesis https://doi.org/10.1093/carcin/bgz113

    Article  Google Scholar 

  • Yu YB, Chen F, Yang YR, Jin YQ, Shi J et al. 2019 lncRNA SNHG16 is associated with proliferation and poor prognosis of pediatric neuroblastoma. Int. J. Oncol. 55 93–102

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan Y, Wang Q, Ma SL, Xu LQ, Liu MY et al. 2019 lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/β-catenin signaling pathway. AM. J. Transl. Res. 11 7104

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang SY and Yu DH 2010 PI (3) king apart PTEN’s role in cancer. Clin. Cancer Res. 16 4325–4330

    Article  CAS  Google Scholar 

  • Zhou XY, Liu H, Ding ZB, Xi HP and Wang GW 2020 lncRNA SNHG16 promotes glioma tumorigenicity through miR-373/EGFR axis by activating PI3K/AKT pathway. Genomics 112 1021–1029

    Article  CAS  Google Scholar 

  • Zhu CL, Cheng D, Qiu XB, Zhuang M and Liu ZW 2018 Long noncoding RNA SNHG16 promotes cell proliferation by sponging microRNA-205 and upregulating ZEB1 expression in osteosarcoma. Cell. Physiol. Biochem. 51 429–440

    Article  CAS  Google Scholar 

  • Zhuang M, Li L and Ma J 2019 LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells. Eur. Rev. Med. Pharmacol. Sci. 23 2908–2915

    PubMed  Google Scholar 

Download references

Funding

This work was supported by the Shaanxi Key R & D Program Project (No. 2018SF-205).

Author information

Authors and Affiliations

  1. School of Medicine, Xi’an Peihua University, 888 Changning Street, Xi’an, 710125, China

    Min Shi, Qi Wei & Lei Chen

  2. Clinical Laboratory, Xi’an Chang’an Hospital, 17 Wenjing Road, Xi’an, 710016, China

    Ruili Yang

  3. Department of Hematology, Xi’an Central Hospital, 161 Xiwu Road, Xi’an, 710003, China

    Jing Lin & Xiaobo Guo

  4. Department of Blood Transfusion, Xi’an Central Hospital, 161 Xiwu Road, Xi’an, 710003, China

    Weifeng Gong

  5. Clinical Laboratory, Xi’an Central Hospital, 161 Xiwu Road, Xi’an, 710003, China

    Yang Li

Authors
  1. Min Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruili Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qi Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weifeng Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaobo Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaobo Guo.

Ethics declarations

Statement of Ethics

All patients and healthy volunteers gave their informed consent to the study and signed the informed consent form. This research was approved by the Ethics Committee of the Xi’an Central Hospital and adhered to the ethical guidelines of the Declaration of Helsinki.

Additional information

Corresponding editor: Sorab Dalal

Supplementary Inforamtion

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, M., Yang, R., Lin, J. et al. LncRNA-SNHG16 promotes proliferation and migration of acute myeloid leukemia cells via PTEN/PI3K/AKT axis through suppressing CELF2 protein. J Biosci 46, 4 (2021). https://doi.org/10.1007/s12038-020-00127-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12038-020-00127-1

Keywords

Search

Navigation