Skip to main content
Log in

Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis

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

Abstract

Long non-coding RNAs (lncRNAs) are associated with colorectal cancer (CRC); however, CRC-related linc00239 functions have not been fully elucidated. Prognostic analysis of patients with CRC with linc00239 overexpression was performed using data from The Cancer Genome Atlas database. Cell Counting Kit-8 and Transwell were used to determine linc00239 functions for CRC cells. The lncRNA–miRNA–mRNA interaction network was used to screen target miRNAs and mRNAs regulated by linc00239. Quantitative real-time polymerase chain reaction and western blotting were used to confirm the miRNA and mRNA expression. Furthermore, a miRNA inhibitor was transfected into CRC cells, and cell function was evaluated. Results indicated a high linc00239 expression in the tumor tissue of patients with CRC. Transfection of linc00239 siRNA into SW480 and LOVO cells decreased cell proliferation, cell migration, and invasion. MiR-182-5p/metadherin (MTDH) axis is a downstream pathway of linc00239. MTDH expression, the activity of cell proliferation, migration, and invasion, which were suppressed by linc00239 siRNA, were partially attenuated when linc00239 siRNA and miR-182-5p inhibitor were co-transfected into the CRC cells. Furthermore, miR-182-5p expression was decreased and MTDH expression was promoted in CRC tissues. Altogether, linc00239 may promote CRC development through the miR-182-5p/MTDH axis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The datasets generated and/or analysed during the current study are available in the [GEPIA] repository [http://gepia.cancer-pku.cn/detail.php?gene=linc00239], [miRanda] software [http://www.mirbase.org/] and mirTarbase repository [http://miRTarBase.cuhk.edu.cn/].

References

  • Abdel Ghafar MT, Soliman NA (2022) Metadherin (AEG-1/MTDH/LYRIC) expression: significance in malignancy and crucial role in colorectal cancer. Adv Clin Chem 106:235–280

    Article  CAS  PubMed  Google Scholar 

  • Cao MQ, You AB, Zhu XD, Zhang W, Zhang YY, Zhang SZ, Zhang KW, Cai H, Shi WK, Li XL, Li KS, Gao DM, Ma DN, Ye BG, Wang CH, Qin CD, Sun HC, Zhang T, Tang ZY (2018) miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a. J Hematol Oncol 11:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao J, Yu U, Li L, Yuan X, Chen S, Xu H, Yi M, Liu S (2022) CircKL inhibits the growth and metastasis of kidney cancer by sponging miR-182-5p and upregulating FBXW7. Oncol Rep 47:1–10

    Article  CAS  Google Scholar 

  • Casimiro S, Fernandes A, Oliveira AG, Franco M, Pires R, Peres M, Matias M, Tato-Costa J, Guerra N, Ramos M, Cruz J, Costa L (2014) Metadherin expression and lung relapse in patients with colorectal carcinoma. Clin Exp Metastasis 31:689–696

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132

    Article  PubMed  Google Scholar 

  • Chen L, Zhang J, Lyu Z, Chen Y, Ji X, Cao H, Jin M, Zhu J, Yang J, Ling R, Xing J, Ren T, Lyu Y (2018) Positive feedback loop between mitochondrial fission and Notch signaling promotes survivin-mediated survival of TNBC cells. Cell Death Dis 9:1050

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng K, Zhao Z, Wang G, Wang J, Zhu W (2018) lncRNA GAS5 inhibits colorectal cancer cell proliferation via the miR-182-5p/FOXO3a axis. Oncol Rep 40:2371–2380

    CAS  PubMed  Google Scholar 

  • Cui M, Chen M, Shen Z, Wang R, Fang X, Song B (2019) LncRNA-UCA1 modulates progression of colon cancer through regulating the miR-28–5p/HOXB3 axis. J Cell Biochem. 120:6926

    Article  CAS  PubMed  Google Scholar 

  • Dai B, Kong DL, Tian J, Liu TW, Zhou H, Wang ZF (2019) microRNA-1205 promotes cell growth by targeting APC2 in lung adenocarcinoma. Eur Rev Med Pharmacol Sci 23:1125–1133

    CAS  PubMed  Google Scholar 

  • Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874

    Article  CAS  PubMed  Google Scholar 

  • Fu XM, Guo W, Li N, Liu HZ, Liu J, Qiu SQ, Zhang Q, Wang LC, Li F, Li CL (2017) The expression and function of long noncoding RNA lncRNA-ATB in papillary thyroid cancer. Eur Rev Med Pharmacol Sci 21:3239–3246

    PubMed  Google Scholar 

  • Gnosa S, Shen YM, Wang CJ, Zhang H, Stratmann J, Arbman G, Sun XF (2012) Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines. J Transl Med 10:109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu MJ, Huang QC, Bao CZ, Li YJ, Li XQ, Ye D, Ye ZH, Chen K, Wang JB (2018) Attributable causes of colorectal cancer in China. BMC Cancer 18:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Han SH, Mo JS, Park WC, Chae SC (2019) Reduced microRNA 375 in colorectal cancer upregulates metadherin-mediated signaling. World J Gastroenterol 25:6495–6507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Y, Gao X, Wu N, Jin Y, Zhou H, Wang W, Liu H, Chu Y, Cao J, Jiang M, Yang S, Shi Y, Xie X, Chen F, Han Y, Qin W, Xu B, Liang J (2022) Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2. Cell Death Dis 13:742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He HT, Xu M, Kuang Y, Han XY, Wang MQ, Yang Q (2016) Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma. Onco Targets Ther 9:6399–6406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21:1253–1261

    Article  CAS  PubMed  Google Scholar 

  • Jia Y, Tian C, Wang H, Yu F, Lv W, Duan Y, Cheng Z, Wang X, Wang Y, Liu T, Wang J, Liu L (2021) Long non-coding RNA NORAD/miR-224-3p/MTDH axis contributes to CDDP resistance of esophageal squamous cell carcinoma by promoting nuclear accumulation of β-catenin. Mol Cancer 20:162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin Y, Zhang ZL, Huang Y, Zhang KN, Xiong B (2019) MiR-182-5p inhibited proliferation and metastasis of colorectal cancer by targeting MTDH. Eur Rev Med Pharmacol Sci 23:1494–1501

    CAS  PubMed  Google Scholar 

  • Jing H, Qu X, Liu L, Xia H (2018) A novel long noncoding RNA (lncRNA), LL22NC03-N64E9.1, promotes the proliferation of lung cancer cells and is a potential prognostic molecular biomarker for lung cancer. Med Sci Monit 24:4317–4323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li WF, Dai H, Ou Q, Zuo GQ, Liu CA (2016) Overexpression of microRNA-30a-5p inhibits liver cancer cell proliferation and induces apoptosis by targeting MTDH/PTEN/AKT pathway. Tumour Biol 37:5885–5895

    Article  CAS  PubMed  Google Scholar 

  • Li JW, Huang CZ, Li JH, Yuan JH, Chen QH, Zhang WF, Xu ZS, Liu YP, Li Y, Zhan MX, Lu LG (2018a) Knockdown of metadherin inhibits cell proliferation and migration in colorectal cancer. Oncol Rep 40:2215–2223

    CAS  PubMed  Google Scholar 

  • Li N, Nan CC, Zhong XY, Weng JQ, Fan HD, Sun HP, Tang S, Shi L, Huang SX (2018b) miR-182-5p promotes growth in oral squamous cell carcinoma by inhibiting CAMK2N1. Cell Physiol Biochem 49:1329–1341

    Article  CAS  PubMed  Google Scholar 

  • Liang B, Zhong Y, Wang B, Lin L, Liu J, Lin X, Huang Y, Hu M, Zhang B, Meng H, Jiang L, Jiang J, Wu J, Zhang Y, Rong W, Yang X, Huang Z (2021) 1,2-Dichloroethane induces apoptosis in the cerebral cortexes of NIH Swiss mice through microRNA-182-5p targeting phospholipase D1 via a mitochondria-dependent pathway. Toxicol Appl Pharmacol 430:115728

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Han Z, Li H, Zhu Y, Sun Z, Zhu A (2018) LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3. Mol Cancer 17:118

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu L, Wang HJ, Meng T, Lei C, Yang XH, Wang QS, Jin B, Zhu JF (2019) lncRNA GAS5 inhibits cell migration and invasion and promotes autophagy by targeting miR-222-3p via the GAS5/PTEN-signaling pathway in CRC. Mol Ther Nucleic Acids 17:644–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Sakurai D, Fujimura L, Kawakami K, Chiyomaru T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, Seki N (2011) Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC). J Hum Genet 56:595–601

    Article  CAS  PubMed  Google Scholar 

  • Shi D, Zheng H, Zhuo C, Peng J, Li D, Xu Y, Li X, Cai G, Cai S (2014) Low expression of novel lncRNA RP11–462C24.1 suggests a biomarker of poor prognosis in colorectal cancer. Med Oncol 31:31

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang Y, Wan W, Wang L, Ji S, Zhang J (2015) microRNA-451 inhibited cell proliferation, migration and invasion through regulation of MIF in renal cell carcinoma. Int J Clin Exp Pathol 8:15611–15621

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45:W98-w102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng YY, Moriarity BS, Gong W, Akiyama R, Tiwari A, Kawakami H, Ronning P, Reuland B, Guenther K, Beadnell TC, Essig J, Otto GM, O’Sullivan MG, Largaespada DA, Schwertfeger KL, Marahrens Y, Kawakami Y, Bagchi A (2014) PVT1 dependence in cancer with MYC copy-number increase. Nature 512:82–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tusa I, Gagliardi S, Tubita A, Pandolfi S, Urso C, Borgognoni L, Wang J, Deng X, Gray NS, Stecca B, Rovida E (2018) ERK5 is activated by oncogenic BRAF and promotes melanoma growth. Oncogene 37:2601–2614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang XD, Lu J, Lin YS, Gao C, Qi F (2019) Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro. World J Gastroenterol 25:1697–1714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Chen H, Wu M, Peng S, Zhang L (2020) Downregulation of miR-182-5p inhibits the proliferation and invasion of triple-negative breast cancer cells through regulating TLR4/NF-κB pathway activity by targeting FBXW7. Ann Transl Med 8:995

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiao H, Tang K, Liu P, Chen K, Hu J, Zeng J, Xiao W, Yu G, Yao W, Zhou H, Li H, Pan Y, Li A, Ye Z, Wang J, Xu H, Huang Q (2015) LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget 6:38005–38015

    Article  PubMed  PubMed Central  Google Scholar 

  • Xue J, Zhou A, Wu Y, Morris SA, Lin K, Amin S, Verhaak R, Fuller G, Xie K, Heimberger AB, Huang S (2016) miR-182-5p induced by STAT3 activation promotes glioma tumorigenesis. Cancer Res 76:4293–4304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Dai W, Sun Y, Zhao Z (2019) Long non-coding RNA linc00239 promotes malignant behaviors and chemoresistance against doxorubicin partially via activation of the PI3K/Akt/mTOR pathway in acute myeloid leukaemia cells. Oncol Rep 41:2311–2320

    CAS  PubMed  Google Scholar 

  • Yu X, Zhao J, He Y (2018) Long non-coding RNA PVT1 functions as an oncogene in human colon cancer through miR-30d-5p/RUNX2 axis. J Buon 23:48–54

    PubMed  Google Scholar 

  • Yu Y, Kou D, Liu B, Huang Y, Li S, Qi Y, Guo Y, Huang T, Qi X, Jia L (2020) LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR-155. Int J Lab Hematol 42:464–472

    Article  PubMed  Google Scholar 

  • Zhang F, Yang Q, Meng F, Shi H, Li H, Liang Y, Han A (2013) Astrocyte elevated gene-1 interacts with β-catenin and increases migration and invasion of colorectal carcinoma. Mol Carcinog 52:603–610

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Zhang Q, Shi G, Yin J (2018) MiR-182-5p regulates BCL2L12 and BCL2 expression in acute myeloid leukemia as a potential therapeutic target. Biomed Pharmacother 97:1189–1194

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Zhou M, Zhao X, Wang G, Li J (2020) Long noncoding RNA LINC00173 is downregulated in cervical cancer and inhibits cell proliferation and invasion by modulating the miR-182-5p/FBXW7 axis. Pathol Res Pract 216:152994

    Article  CAS  PubMed  Google Scholar 

  • Zhao YS, Yang WC, Xin HW, Han JX, Ma SG (2019) MiR-182-5p knockdown targeting PTEN inhibits cell proliferation and invasion of breast cancer cells. Yonsei Med J 60:148–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

The study was supported by the [Medical Science and Technology Research Foundation of Guangdong Province, China] (Grant Number [A2021326]).

Author information

Authors and Affiliations

Authors

Contributions

JG and TX performed experiments and contributed to interpretation of data; JG wrote the original daft; SZ contributed to the project administration, data analysis, and funding acquisition; All authors contributed to design of the work, revised manuscript, and approved the final manuscript.

Corresponding author

Correspondence to Shi Zhang.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics Approval and Consent to Participate

Not applicable.

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.

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

Guo, J., Xie, T. & Zhang, S. Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10510-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-023-10510-w

Keywords

Navigation