Skip to main content

Advertisement

SpringerLink
Log in

LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Hepatoblastoma (HB) is a common primary liver malignant tumor in children. Long non-coding RNAs (lncRNAs) are closely engaged in HB progression. The role and regulatory molecule mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in HB remain unclear. Through qRT-PCR or western blot, we found that SNHG1 and proviral integration site for moloney murine leukemia virus 3 (PIM3) were elevated but miR-6838-5p was decreased in HB cells. Cell biology experiments revealed that SNHG1 depletion or miR-6838-5p upregulation suppressed cell proliferation, migration, and invasion of HB cells. Mechanistically, luciferase activity assay validated that miR-6838-5p could interact with SNHG1 or PIM3. SNHG1 up-regulated PIM3 expression via sponging miR-6838-5p. Moreover, miR-6838-5p inhibitor abolished SNHG1 depletion-mediated suppression of malignant behaviors in HB cells. PIM3 overexpression neutralized miR-6838-5p mimics-mediated repression of malignant phenotypes in HB cells. Furthermore, miR-6838-5p overexpression suppressed RhoA activation, which was restored by PIM3 upregulation. What’s more, the results at the cellular level were further verified by nude mice tumor formation experiment. In conclusion, SNHG1 regulated miR-6838-5p/PIM3/RhoA axis to promote malignant phenotypes of HB, which might provide novel therapeutic target for HB treatment.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

CCK-8:

Cell counting kit-8

ceRNAs:

Competitive endogenous RNAs

HB:

Hepatoblastoma

LncRNAs:

Long non-coding RNAs

MiRNAs:

MicroRNAs

PIM3:

Proviral integration site for Moloney murine leukemia virus 3

RhoA:

Ras homolog gene family, member A

SNHG1:

Small nucleolar RNA host gene 1

References

  • Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ (2020) Regulatory mechanism of MicroRNA expression in cancer. Int J Mol Sci. https://doi.org/10.3390/ijms21051723

    Article  PubMed  PubMed Central  Google Scholar 

  • BhanSoleimani AM, Mandal SS (2017) Long noncoding RNA and cancer: a new paradigm. Cancer Res 77:3965–3981

    Article  Google Scholar 

  • Cai H, Xu H, Lu H, Xu W, Liu H, Wang X et al (2022) LncRNA SNHG1 facilitates tumor proliferation and represses apoptosis by regulating PPARγ ubiquitination in bladder cancer. Cancers (basel). https://doi.org/10.3390/cancers14194740

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen J, Wang F, Xu H, Xu L, Chen D, Wang J et al (2020) Long non-coding RNA SNHG1 regulates the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways via EZH2 to affect the proliferation, apoptosis, and autophagy of prostate cancer cell. Front Oncol 10:552907

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen Z, Gong Q, Li D, Zhou J (2022) CircKIAA0368 Promotes Proliferation, Migration, and Invasion by Upregulating HOXA10 in Nasopharyngeal Carcinoma. Am J Rhinol Allergy. https://doi.org/10.1177/19458924221100960

    Article  PubMed  Google Scholar 

  • Dang Y, Jiang N, Wang H, Chen X, Gao Y, Zhang X et al (2020) Proto-oncogene serine/threonine kinase pim3 promotes cell migration via modulating rho GTPase signaling. J Proteome Res 19:1298–1309

    Article  CAS  PubMed  Google Scholar 

  • Dong R, Liu GB, Liu BH, Chen G, Li K, Zheng S et al (2016) Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma. Cell Death Dis 7:e2278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan Y, Wu H, Hao X, Li F, Liu J, Zhu C et al (2021) Knockdown of long non-coding MIR210HG inhibits cell proliferation, migration, and invasion in hepatoblastoma via the microRNA-608-FOXO6 axis. J Int Med Res 49:3000605211054695

    Article  CAS  PubMed  Google Scholar 

  • Hsu CL, Yin CF, Chang YW, Fan YC, Lin SH, Wu YC et al (2022) LncRNA SNHG1 regulates neuroblastoma cell fate via interactions with HDAC1/2. Cell Death Dis 13:809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Q, Yang Z, Tian JH, You PD, Wang J, Ma R et al (2022) LncSNHG1 promoted CRC proliferation through the miR-181b-5p/SMAD2 Axis. J Oncol 2022:4181730

    PubMed  PubMed Central  Google Scholar 

  • Jiang X, Yuan Y, Tang L, Wang J, Liu Q, Zou X et al (2021) Comprehensive pan-cancer analysis of the prognostic and immunological roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C axis. Front Cell Dev Biol 9:765772

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalish JM, Doros L, Helman LJ, Hennekam RC, Kuiper RP, Maas SM et al (2017) Surveillance recommendations for children with overgrowth syndromes and predisposition to wilms tumors and hepatoblastoma. Clin Cancer Res 23:e115–e122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LeeDutta YSA (2009) MicroRNAs in cancer. Annu Rev Pathol 4:199–227

    Article  Google Scholar 

  • Li W, Dong X, He C, Tan G, Li Z, Zhai B et al (2019) LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J Exp Clin Cancer Res 38:183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang C, Yu XJ, Guo XZ, Sun MH, Wang Z, Song Y et al (2015) MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine. Oncotarget 6:14440–14455

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Yang Y, Li L, Liu Y, Geng P, Li G et al (2018) LncRNA SNHG1 enhances cell proliferation, migration, and invasion in cervical cancer. Biochem Cell Biol 96:38–43

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Wang P, Zhang H (2019) MiR-6838-5p suppresses cell metastasis and the EMT process in triple-negative breast cancer by targeting WNT3A to inhibit the Wnt pathway. J Gene Med 21:e3129

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Wang L, Li X, Tian P, Xu H, Li Z et al (2019a) Effect of miR-21 on apoptosis in hepatoblastoma cell through activating ASPP2/p38 signaling pathway in vitro and in vivo. Artif Cells Nanomed Biotechnol 47:3729–3736

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Wang J, Sun G, Wu Q, Ma J, Zhang X et al (2019b) m(6)A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Mol Cancer 18:188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu G, Liu B, Liu X, Xie L, He J, Zhang J et al (2021) ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3. J Cell Mol Med 25:3524–3536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu G, Zhu Q, Wang H, Zhou J, Jiang B (2022a) Long non-coding RNA Linc00205 promotes hepatoblastoma progression through regulating microRNA-154-3p/Rho-associated coiled-coil Kinase 1 axis via mitogen-activated protein kinase signaling. Aging (albany NY) 14:1782–1796

    Article  CAS  PubMed  Google Scholar 

  • Liu B, Chen J, Shang F, Lian M, Shen X, Fang J (2022b) Tumor-derived exosome FGD5-AS1 promotes angiogenesis, vascular permeability, and metastasis in thyroid cancer by targeting the miR-6838-5p/VAV2 Axis. J Oncol 2022:4702855

    PubMed  PubMed Central  Google Scholar 

  • Liu Q, Luo J, Wang H, Zhang L, Jin G (2022c) SNHG1 functions as an oncogenic lncRNA and promotes osteosarcoma progression by up-regulating S100A6 via miR-493-5p. Acta Biochim Biophys Sin (shanghai) 54:137–147

    Article  PubMed  Google Scholar 

  • Lu X, Hu K, TanZhao QK (2022) Silencing SNHG1 suppresses viability, proliferation and invasion of gallbladder carcinoma cells via targeting miR-194-5p. Ann Clin Lab Sci 52:707–720

    CAS  PubMed  Google Scholar 

  • Marayati R, Stafman LL, Williams AP, Bownes LV, Quinn CH, Aye JM et al (2021) PIM kinases mediate resistance to cisplatin chemotherapy in hepatoblastoma. Sci Rep 11:5984

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Marayati R, Stafman LL, Williams AP, Bownes LV, Quinn CH, Markert HR et al (2022) CRISPR/Cas9-mediated knockout of PIM3 suppresses tumorigenesis and cancer cell stemness in human hepatoblastoma cells. Cancer Gene Ther 29:558–572

    Article  CAS  PubMed  Google Scholar 

  • Min J, Ma J, Wang QYuD (2022) Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription. Clinics (sao Paulo) 77:100081

    Article  PubMed  Google Scholar 

  • Panchal NK, Sabina EP (2020) A serine/threonine protein PIM kinase as a biomarker of cancer and a target for anti-tumor therapy. Life Sci 255:117866

    Article  CAS  PubMed  Google Scholar 

  • Sharma D, Subbarao G, Saxena R (2017) Hepatoblastoma. Semin Diagn Pathol 34(192):200

    Google Scholar 

  • Shen R, Wang X, Wang S, Zhu D, Li M (2021) Long noncoding RNA CERS6-AS1 accelerates the proliferation and migration of pancreatic cancer cells by sequestering MicroRNA-15a-5p and MicroRNA-6838-5p and modulating HMGA1. Pancreas 50:617–624

    Article  CAS  PubMed  Google Scholar 

  • Stafman LL, Waldrop MG, Williams AP, Aye JM, Stewart JE, Mroczek-Musulman E et al (2019) The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival. J Pediatr Surg 54:1206–1213

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan X, Chen WB, Lv DJ, Yang TW, Wu KH, Zou LB et al (2021) LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer. Cell Death Dis 12:138

    Article  PubMed  PubMed Central  Google Scholar 

  • Thomson DW, Dinger ME (2016) Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 17:272–283

    Article  CAS  PubMed  Google Scholar 

  • Trobaugh-Lotrario AD, Katzenstein HM (2012) Chemotherapeutic approaches for newly diagnosed hepatoblastoma: past, present, and future strategies. Pediatr Blood Cancer 59:809–812

    Article  PubMed  Google Scholar 

  • Wang L, Cho KB, Li Y, Tao G, Xie Z, Guo B (2019) Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms20225758

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang XD, Peng JB, Zhou CY, Que Q, Li HY, He Y et al (2020) Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles. Oncol Rep 43:1915–1927

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, He Y, Mackowiak B, Gao B (2021) MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 70:784–795

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Chu E, Kang Y (2021) PIM kinases in multiple myeloma. Cancers (basel). https://doi.org/10.3390/cancers13174304

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu M, Chen X, Lin K, Zeng K, Liu X, Pan B et al (2018) The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer 17:141

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu X, Wang S, Wang H, Pan C, Yang WYuJ (2021) Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion. BMC Cancer 21:1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye ZH, Gui DW, Wang XY, Wang JFuJL (2022) LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR-103a. J Clin Lab Anal 36:e24422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, Yang L, Hou L, Tang X (2021) LncRNA SNHG1 promotes tumor progression and cisplatin resistance through epigenetically silencing miR-381 in breast cancer. Bioengineered 12:9239–9250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Liang F, Li Q, Sun H, Li F, Jiao Z et al (2022) LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway. Biol Direct 17:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhi T, Zhang WL, Zhang Y, WangHuang YZDS (2021) Prevalence, clinical features and prognosis of malignant solid tumors in infants: a 14-year study. Bosn J Basic Med Sci 21:598–606

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou W, Ding X, JinLi PP (2020) miR-6838-5p affects cell growth, migration, and invasion by targeting GPRIN3 via the Wnt/β-catenin signaling pathway in gastric cancer. Pathobiology 87:327–337

    Article  CAS  PubMed  Google Scholar 

  • Zhu C, He X, Chen K, Huang Z, Yao A, Tian X et al (2021) LncRNA NBR2 aggravates hepatoblastoma cell malignancy and promotes cell proliferation under glucose starvation through the miR-22/TCF7 axis. Cell Cycle 20:575–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by LncRNA SNHG1 regulates the proliferation, migration, invasion and apoptosis of hepatoblastoma through PIM3/RhoA axis (202206023841).

Author information

Authors and Affiliations

  1. General Surgery, Hunan Children’s Hospital, No. 86, ZiYuan Road, Yuhua District, Changsha, 410007, Hunan Province, People’s Republic of China

    Tian Zhang, Chunyi Ji, Yanbing Zhang, Miaoxian Yuan, Hongqiang Gao & Qiang Yin

Authors
  1. Tian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunyi Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanbing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miaoxian Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hongqiang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiang Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TZ and QY wrote the main manuscript text and CJ, YZ, MY and HG prepared figures. All authors reviewed the manuscript.

Corresponding author

Correspondence to Qiang Yin.

Ethics declarations

Conflict of interests

These authors declared no competing interests in this work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, T., Ji, C., Zhang, Y. et al. LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis. Biochem Genet 62, 59–76 (2024). https://doi.org/10.1007/s10528-023-10404-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-023-10404-x

Keywords

Search

Navigation