Skip to main content
SpringerLink
Log in

Long Non-coding RNA LOXL1-AS1 Facilitates Colorectal Cancer Progression via Regulating miR-1224-5p/miR-761/HK2 Axis

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

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Long non-coding RNAs (lncRNAs) play crucial roles in the development of malignant tumors. The present study aimed to explore the function and potential mechanism of lncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) in CRC. The abundance of LOXL1-AS1, miR-1224-5p, miR-761, and hexokinase 2 (HK2) was detected by quantitative real-time PCR or western blot assay. Cell proliferation was assessed by Cell Counting Kit-8 and colony formation assays. Cell apoptosis, invasion, and migration were examined by flow cytometry, transwell assay, and wound healing assay. Glycolysis was evaluated by detecting glucose consumption, lactate production, and ATP/ADP ratios. Xenograft assay was used for in vivo tumor growth analysis. LOXL1-AS1 and HK2 levels were increased, while miR-1224-5p and miR-761 levels were reduced in CRC tissues and cells. Knockdown of LOXL1-AS1 suppressed CRC cell proliferation, invasion, migration, and glycolysis, and induced cell apoptosis. Silencing of LOXL1-AS1 blocked tumor growth in vivo. Moreover, LOXL1-AS1 accelerated CRC cell progression by absorbing miR-1224-5p/miR-761. Besides, miR-1224-5p and miR-761 inhibited CRC cell progression via targeting HK2. LOXL1-AS1 contributed to CRC progression via modulating miR-1224-5p/miR-761/HK2 pathway.

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
Fig. 9

Similar content being viewed by others

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  • Brenner H, Kloor M, Pox CP (2014) Colorectal cancer. Lancet 383:1490–1502

    Article  PubMed  Google Scholar 

  • Chan JJ, Tay Y (2018) Noncoding RNA: RNA regulatory networks in cancer. Int J Mol Sci 19:1310

    Article  PubMed Central  Google Scholar 

  • Chen S, Li W, Guo A (2019) LOXL1-AS1 predicts poor prognosis and promotes cell proliferation, migration, and invasion in osteosarcoma. Biosci Rep 39:4

    Google Scholar 

  • Chen C, Wei M, Wang C, Sun D, Liu P, Zhong X, Yu W (2020) Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2. Aging (albany NY) 12:11685–11697

    Article  CAS  Google Scholar 

  • Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB (2019) Colorectal cancer. Lancet 394:1467–1480

    Article  PubMed  Google Scholar 

  • Evans JR, Feng FY, Chinnaiyan AM (2016) The bright side of dark matter: lncRNAs in cancer. J Clin Invest 126:2775–2782

    Article  PubMed  PubMed Central  Google Scholar 

  • Ganapathy-Kanniappan S (2018) Molecular intricacies of aerobic glycolysis in cancer: current insights into the classic metabolic phenotype. Crit Rev Biochem Mol Biol 53:667–682

    Article  CAS  PubMed  Google Scholar 

  • Ganapathy-Kanniappan S, Geschwind JF (2013) Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 12:152

    Article  PubMed  PubMed Central  Google Scholar 

  • Garcia SN, Guedes RC, Marques MM (2019) Unlocking the potential of HK2 in cancer metabolism and therapeutics. Curr Med Chem 26:7285–7322

    Article  CAS  PubMed  Google Scholar 

  • He Q, Long J, Yin Y, Li Y, Lei X, Li Z, Zhu W (2019) Emerging roles of lncRNAs in the formation and progression of colorectal cancer. Front Oncol 9:1542

    Article  PubMed  Google Scholar 

  • He G, Yao W, Li L, Wu Y, Feng G, Chen L (2020) LOXL1-AS1 contributes to the proliferation and migration of laryngocarcinoma cells through miR-589-5p/TRAF6 axis. Cancer Cell Int 20:504

    Article  PubMed  PubMed Central  Google Scholar 

  • Hong YG, Huang ZP, Liu QZ, Gao XH, Xin C, Zhang W, Li P, Hao LQ (2020) MicroRNA-95-3p inhibits cell proliferation and metastasis in colorectal carcinoma by HDGF. Biomed J 43:163–173

    Article  PubMed  PubMed Central  Google Scholar 

  • Jarroux J, Morillon A, Pinskaya M (2017) History, discovery, and classification of lncRNAs. Adv Exp Med Biol 1008:1–46

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y, Shinjo K, Katsushima K (2017) Long non-coding RNAs as an epigenetic regulator in human cancers. Cancer Sci 108:1927–1933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krasnov GS, Dmitriev AA, Lakunina VA, Kirpiy AA, Kudryavtseva AV (2013) Targeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy. Expert Opin Ther Targets 17:1221–1233

    Article  CAS  PubMed  Google Scholar 

  • Li C, Yu Z, Ye J (2020a) MicroRNA-513a-3p regulates colorectal cancer cell metabolism via targeting hexokinase 2. Exp Ther Med 20:572–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Peng W, Yang P, Chen R, Gu Q, Qian W, Ji D, Wang Q, Zhang Z, Tang J, Sun Y (2020b) MicroRNA-1224-5p inhibits metastasis and epithelial-mesenchymal transition in colorectal cancer by targeting SP1-mediated NF-kappaB signaling pathways. Front Oncol 10:294

    Article  PubMed  PubMed Central  Google Scholar 

  • Li W, Zhang B, Jia Y, Shi H, Wang H, Guo Q, Li H (2020c) LncRNA LOXL1-AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR-423-5p and targeting MYBL2. Cancer Med 9:689–699

    Article  CAS  PubMed  Google Scholar 

  • Lin YH (2020) Crosstalk of lncRNA and cellular metabolism and their regulatory mechanism in cancer. Int J Mol Sci 21:2947

    Article  CAS  PubMed Central  Google Scholar 

  • Liu FQ, Cai SJ (2019) Adjuvant and perioperative neoadjuvant therapy for colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi 22:315–320

    CAS  PubMed  Google Scholar 

  • Liu Y, Guo C, Li F, Wu L (2020) LncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates pancreatic cancer progression. Cell Biochem Funct 38:58–65

    Article  CAS  PubMed  Google Scholar 

  • Mathupala SP, Ko YH, Pedersen PL (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25:4777–4786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren Y, Shi G, Jiang P, Meng Q (2019) MicroRNA-761 is downregulated in colorectal cancer and regulates tumor progression by targeting Rab3D. Exp Ther Med 17:1841–1846

    CAS  PubMed  Google Scholar 

  • Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29:452–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon K (2016) Colorectal cancer development and advances in screening. Clin Interv Aging 11:967–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun H, Huang Z, Sheng W, Xu MD (2018) Emerging roles of long non-coding RNAs in tumor metabolism. J Hematol Oncol 11:106

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun Q, Li J, Li F, Li H, Bei S, Zhang X, Feng L (2019) LncRNA LOXL1-AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR-708–5p/USF1 pathway. Cell Prolif 52:e12687

    Article  PubMed  PubMed Central  Google Scholar 

  • Tam C, Wong JH, Tsui SKW, Zuo T, Chan TF, Ng TB (2019) LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years. Appl Microbiol Biotechnol 103:4649–4677

    Article  CAS  PubMed  Google Scholar 

  • Thomas M, Lieberman J, Lal A (2010) Desperately seeking microRNA targets. Nat Struct Mol Biol 17:1169–1174

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Cui F, Chen Y, Zhu Y, Liu F (2020a) Long non-coding RNA LOXL1-AS1 enhances colorectal cancer proliferation, migration and invasion through miR-708-5p/CD44-EGFR axis. Onco Targets Ther 13:7615–7627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Yan F, Wang L, Sun G, Liu J, Qu M, Wang Y, Li T (2020b) MicroRNA: another pharmacological avenue for colorectal cancer? Front Cell Dev Biol 8:812

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie YH, Chen YX, Fang JY (2020) Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 5:22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong W, Yang S, Zhang W, Chen Y, Wang F (2019) MiR-761 inhibits colorectal cancer cell proliferation and invasion through targeting HDAC1. Pharmazie 74:111–114

    CAS  PubMed  Google Scholar 

  • Xue F, Xu YH, Shen CC, Qin ZL, Zhou HB (2020) Non-coding RNA LOXL1-AS1 exhibits oncogenic activity in ovarian cancer via regulation of miR-18b-5p/VMA21 axis. Biomed Pharmacother 125:109568

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Zhou M, Zou L, Miao J, Wang Y, Li Y, Lu S, Yu J (2019) Long non-coding RNA LOXL1-AS1 acts as a ceRNA for miR-324-3p to contribute to cholangiocarcinoma progression via modulation of ATP-binding cassette transporter A1. Biochem Biophys Res Commun 513:827–833

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Xu J, Zhang H, Sun J, Li N, Huang X (2020) MicroRNA-758 acts as a tumor inhibitor in colorectal cancer through targeting PAX6 and regulating PI3K/AKT pathway. Oncol Lett 19:3923–3930

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None.

Funding

This study was funded by Clinical Science Foundation of Anhui Medical University (Grant No. 2019xkj160) and National and provincial key specialty construction plan (Grant No. Z155080000004).

Author information

Author notes

  1. Tao Guo and Shihao Peng are the co-first author.

Authors and Affiliations

  1. Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Xinzhan District, Hefei City, 230011, Anhui Province, China

    Tao Guo, Shihao Peng, Defeng Liu & Yangyang Li

Authors
  1. Tao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shihao Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Defeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yangyang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Clinical data collection, genetic counseling, and follow-up were performed by TG. Data analyses were performed by SP and DL. The methodology was performed by YL. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tao Guo.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest.

Ethical Approval and Consent to Participate

The design of this protocol follows the tenets of the Declaration of Helsinki, approved by the Ethics Committee of The Fourth Affiliated Hospital of Anhui Medical University.

Patient Consent for Publication

Not applicable.

Additional information

Publisher's Note

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

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, T., Peng, S., Liu, D. et al. Long Non-coding RNA LOXL1-AS1 Facilitates Colorectal Cancer Progression via Regulating miR-1224-5p/miR-761/HK2 Axis. Biochem Genet 60, 2416–2433 (2022). https://doi.org/10.1007/s10528-022-10226-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-022-10226-3

Keywords

Search

Navigation