Skip to main content
SpringerLink
Log in

CircLPAR3 Acts as an Oncogene in Oral Squamous Cell Carcinoma Through Regulating the miR-643/HMGB2 Network

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

Abstract

The malignant progression of oral squamous cell carcinoma (OSCC) has been confirmed to be mediated by a variety of factors, including circular RNA (circRNA). However, the role of circLPAR3 in OSCC development is still unclear. 70 paired OSCC tissues and normal control tissues were obtained from 70 OSCC patients. Quantitative real-time PCR was used to detect the expression of circLPAR3, microRNA (miR)-643, and high-mobility group box 2 (HMGB2). Cell proliferation, apoptosis, metastasis and stemness were assessed using cell counting kit 8 assay, colony-formation assay, flow cytometry, transwell assay and sphere formation assay. Marker protein expression and HMGB2 protein expression were determined by western blot analysis. The interaction between miR-643 and circLPAR3 or HMGB2 was confirmed by RNA pull-down assay, dual-luciferase reporter and RIP assay. The role of circLPAR3 in OSCC tumorigenesis was explored by constructing the xenograft models. Our data showed that circLPAR3 was highly expressed in OSCC tissues and cells. CircLPAR3 silencing suppressed OSCC cell proliferation, metastasis and stemness, while promoted apoptosis. On the mechanism, we discovered that circLPAR3 could sponge miR-643 to positive regulate HMGB2. MiR-643 overexpression had an inhibition effect on OSCC progression, and its inhibitor could reverse the negative regulation of circLPAR3 knockdown on OSCC progression. In addition, overexpressed HMGB2 also reversed the suppressive effect of circLPAR3 silencing on OSCC progression. Animal experiments results showed that downregulated circLPAR3 repressed OSCC tumorigenesis in vivo. Taken together, our data showed that circLPAR3 contributed to OSCC malignant progression through regulating the miR-643/HMGB2 axis.

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

References

  • Bossi P, Alfieri S, Strojan P, Takes RP, Lopez F, Makitie A et al (2019) Prognostic and predictive factors in recurrent and/or metastatic head and neck squamous cell carcinoma: a review of the literature. Crit Rev Oncol Hematol 137:84–91

    Article  Google Scholar 

  • Chang J, Tan W, Ling Z, Xi R, Shao M, Chen M et al (2017) Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations. Nat Commun 8:15290

    Article  CAS  Google Scholar 

  • Chen X, Yu J, Tian H, Shan Z, Liu W, Pan Z et al (2019) Circle RNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cells growth via Glucose transporter-1 (GLUT1) and glycolysis. J Cell Physiol 234(11):19130–19140

    Article  CAS  Google Scholar 

  • Cheng H, Jiang W, Song Z, Li T, Li Y, Zhang L et al (2020) Circular RNA circLPAR3 facilitates esophageal squamous cell carcinoma progression through upregulating HMGB1 via sponging miR-375/miR-433. Onco Targets Ther 13:7759–7771

    Article  CAS  Google Scholar 

  • Cui G, Cai F, Ding Z, Gao L (2019) HMGB2 promotes the malignancy of human gastric cancer and indicates poor survival outcome. Hum Pathol 84:133–141

    Article  CAS  Google Scholar 

  • Fridman E, Na’ara S, Agarwal J, Amit M, Bachar G, Villaret AB et al (2018) The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: an international collaborative study. Cancer 124(14):2948–2955

    Article  Google Scholar 

  • Gamez ME, Kraus R, Hinni ML, Moore EJ, Ma DJ, Ko SJ et al (2018) Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults. Oral Oncol 87:43–48

    Article  Google Scholar 

  • Gao L, Zhao C, Li S, Dou Z, Wang Q, Liu J et al (2019) Circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma. Mol Carcinog 58(10):1783–1794

    Article  CAS  Google Scholar 

  • Hamakawa H, Nakashiro K, Sumida T, Shintani S, Myers JN, Takes RP et al (2008) Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer. Head Neck 30(6):800–809

    Article  Google Scholar 

  • He ZH, Guo F, Hu XX, Luo ZY, Yi JW (2020) Knockdown of HMGB2 inhibits proliferation and invasion of renal tumor cells via the p-38MAPK pathway. Eur Rev Med Pharmacol Sci 24(9):4729–4737

    PubMed  Google Scholar 

  • Lei B, Tian Z, Fan W, Ni B (2019) Circular RNA: a novel biomarker and therapeutic target for human cancers. Int J Med Sci 16(2):292–301

    Article  CAS  Google Scholar 

  • Liang C, Wang J, Liu A, Wu Y (2021) Tumor promoting long non-coding RNA CASC15 affects HMGB2 expression by sponging miR-582–5p in colorectal cancer. J Gene Med 4:e3308

    Google Scholar 

  • Lin X, Chen Y (2018) Identification of potentially functional CircRNA-miRNA-mRNA regulatory network in hepatocellular carcinoma by integrated microarray analysis. Med Sci Monit Basic Res 24:70–78

    Article  Google Scholar 

  • Liu L, Chen J, Cai X, Yao Z, Huang J (2019) Progress in targeted therapeutic drugs for oral squamous cell carcinoma. Surg Oncol 31:90–97

    Article  Google Scholar 

  • Lopez-Rosas I, Lopez-Camarillo C, Salinas-Vera YM, Hernandez-de la Cruz ON, Palma-Flores C, Chavez-Munguia B et al (2018) Entamoeba histolytica up-regulates MicroRNA-643 to promote apoptosis by targeting XIAP in human epithelial colon cells. Front Cell Infect Microbiol 8:437

    Article  CAS  Google Scholar 

  • McCauley MJ, Zimmerman J, Maher LJ 3rd, Williams MC (2007) HMGB binding to DNA: single and double box motifs. J Mol Biol 374(4):993–1004

    Article  CAS  Google Scholar 

  • Meng Y, Zhao EY, Zhou Y, Qiang DX, Wang S, Shi L et al (2020) Circular RNA hsa_circ_0011946 promotes cell growth, migration, and invasion of oral squamous cell carcinoma by upregulating PCNA. Eur Rev Med Pharmacol Sci 24(3):1226–1232

    CAS  PubMed  Google Scholar 

  • Panarese I, Aquino G, Ronchi A, Longo F, Montella M, Cozzolino I et al (2019) Oral and oropharyngeal squamous cell carcinoma: prognostic and predictive parameters in the etiopathogenetic route. Expert Rev Anticancer Ther 19(2):105–119

    Article  CAS  Google Scholar 

  • Shao Y, Song Y, Xu S, Li S, Zhou H (2020) Expression profile of circular RNAs in oral squamous cell carcinoma. Front Oncol 10:533616

    Article  Google Scholar 

  • Sheng R, Li X, Wang Z, Wang X (2020) Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer. Cancer Lett 473:139–147

    Article  CAS  Google Scholar 

  • Shi Y, Fang N, Li Y, Guo Z, Jiang W, He Y et al (2020) Circular RNA LPAR3 sponges microRNA-198 to facilitate esophageal cancer migration, invasion, and metastasis. Cancer Sci 111(8):2824–2836

    Article  CAS  Google Scholar 

  • Su W, Shen Y, Wang Y, Wang F, Hong X, Chen Y et al (2021) CircPHIP promotes oral squamous cell carcinoma progression by sponging miR-142-5p and regulating PHIP and ACTN4 expression. Mol Ther Nucleic Acids 23:185–199

    Article  CAS  Google Scholar 

  • Syed N, Chavan S, Sahasrabuddhe NA, Renuse S, Sathe G, Nanjappa V et al (2015) Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. Proteomics 15(2–3):383–393

    Article  CAS  Google Scholar 

  • Wang H, Xing D, Ren D, Feng W, Chen Y, Zhao Z et al (2017) MicroRNA643 regulates the expression of ZEB1 and inhibits tumorigenesis in osteosarcoma. Mol Med Rep 16(4):5157–5164

    Article  CAS  Google Scholar 

  • Wu ZB, Cai L, Lin SJ, Xiong ZK, Lu JL, Mao Y et al (2013) High-mobility group box 2 is associated with prognosis of glioblastoma by promoting cell viability, invasion, and chemotherapeutic resistance. Neuro Oncol 15(9):1264–1275

    Article  CAS  Google Scholar 

  • Xiao M, Song H, You Y, Liu M, Yang X, Wang Y (2021) Metastasis of oral squamous cell carcinoma to the parotid lymph nodes. Int J Oral Maxillofac Surg 50(4):437–443

    Article  CAS  Google Scholar 

  • Xu F, Ni M, Li J, Cheng J, Zhao H, Zhao J et al (2020) Circ0004390 promotes cell proliferation through sponging miR-198 in ovarian cancer. Biochem Biophys Res Commun 526(1):14–20

    Article  CAS  Google Scholar 

  • Yang G, Zhang Y, Yang J (2019) Identification of potentially functional CircRNA-miRNA-mRNA regulatory network in gastric carcinoma using bioinformatics analysis. Med Sci Monit 25:8777–8796

    Article  CAS  Google Scholar 

  • Yang Y, Ci HS, Mao YL, Li JW, Zuo JH (2020) CircRNA_002178 promotes the proliferation and migration of oral squamous cell carcinoma cells by activating the Akt/mTOR pathway. Eur Rev Med Pharmacol Sci 24(11):6122–6130

    CAS  PubMed  Google Scholar 

  • Yue P, Rong X, Zhuang X, Sha HJ, Li JM, Xin L et al (2014) Cloning and expression analysis of a novel high-mobility group box 2 homologue from Lampetra japonica. Fish Physiol Biochem 40(2):625–634

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Peking University Stomatological Hospital, Beijing, 100081, China

    Yunxia Fu, Chunyan Qiu, Yanjun Yang, Jianying Lu & Yun Qi

  2. Maxillofacial Surgery Department, Peking University International Hospital, Beijing, 102206, China

    Yunxia Fu, Chunyan Qiu, Yanjun Yang, Jianying Lu & Yun Qi

  3. Maxillofacial Surgery Ward, Peking University Stomatological Hospital, Peking University International Hospital, No. 22, Zhongguancun South Street, Haidian District, Beijing, 100081, China

    Yunxia Fu

Authors
  1. Yunxia Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunyan Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanjun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianying Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yunxia Fu.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, Y., Qiu, C., Yang, Y. et al. CircLPAR3 Acts as an Oncogene in Oral Squamous Cell Carcinoma Through Regulating the miR-643/HMGB2 Network. Biochem Genet 60, 882–898 (2022). https://doi.org/10.1007/s10528-021-10134-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-021-10134-y

Keywords

Search

Navigation