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BMC Cancer

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Open Access 01-12-2021 | Colon Cancer | Research article

LINC01287 facilitates proliferation, migration, invasion and EMT of colon cancer cells via miR-4500/MAP3K13 pathway

Authors: Dazhi Fu, Yongjun Ren, Chunxiao Wang, Lei Yu, Rui Yu

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Accumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. In the present study, long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear.

Methods

Transcriptome RNA-sequencing was conducted to identify dysregulated lncRNAs. Expression of LINC01287 was evaluated by real-time quantitative PCR. The downstream targets of LINC01287 and miR-4500 were verified by luciferase reporter assay, pull down assay and western blot. The potential functions of LINC01287 were evaluated by cell viability assay, colony formation assay, soft agar assay, flow cytometry, transwell migration and invasion assay, and tumor xenograft growth in colon cancer cells.

Results

Our results indicated that LINC01287 was up-regulated in colon cancer patients. High LINC01287 expression was associated with advanced TNM stage, lymph node metastasis, distant metastasis and shorter overall survival. Knockdown of LINC01287 inhibited cell growth, colony formation in plates and soft agar, transwell cell migration and invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells, while LINC01287 overexpression had contrary effects. In addition, LINC01287 mediated MAP3K13 expression by sponging miR-4500, thus promoted NF-κB p65 phosphorylation. Restored MAP3K13 expression or miR-4500 knockdown partially abrogated the effects of silencing LINC01287 in colon cancer cells.

Conclusion

Our findings demonstrated that the LINC01287/miR-4500/MAP3K13 axis promoted progression of colon cancer. Therefore, LINC01287 might be a potential therapeutic target and prognostic marker for colon cancer patients.

Available only for authorised users

Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019;16(12):713–32. https://doi.org/10.1038/s41575-019-0189-8.CrossRefPubMed

Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394(10207):1467–80. https://doi.org/10.1016/S0140-6736(19)32319-0.CrossRefPubMed

Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59(6):366–78. https://doi.org/10.3322/caac.20038.CrossRefPubMed

Williams CD, Grady WM, Zullig LL. Use of NCCN guidelines, other guidelines, and biomarkers for colorectal Cancer screening. J Natl Compr Cancer Netw. 2016;14(11):1479–85. https://doi.org/10.6004/jnccn.2016.0154.CrossRef

Wang N, Lu Y, Khankari NK, Long J, Li HL, Gao J, et al. Evaluation of genetic variants in association with colorectal cancer risk and survival in Asians. Int J Cancer. 2017;141(6):1130–9. https://doi.org/10.1002/ijc.30812.CrossRefPubMedPubMedCentral

Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, et al. Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. Proc Natl Acad Sci U S A. 2016;113(5):1273–8. https://doi.org/10.1073/pnas.1500992113.CrossRefPubMedPubMedCentral

Flynn RA, Chang HY. Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell. 2014;14(6):752–61. https://doi.org/10.1016/j.stem.2014.05.014.CrossRefPubMedPubMedCentral

Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307. https://doi.org/10.1016/j.cell.2013.02.012.CrossRefPubMedPubMedCentral

Tang J, Yan T, Bao Y, Shen C, Yu C, Zhu X, et al. LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc. Nat Commun. 2019;10(1):3499. https://doi.org/10.1038/s41467-019-11447-8.CrossRefPubMedPubMedCentral

10.

Mo Y, He L, Lai Z, Wan Z, Chen Q, Pan S, et al. LINC01287/miR-298/STAT3 feedback loop regulates growth and the epithelial-to-mesenchymal transition phenotype in hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2018;37(1):149. https://doi.org/10.1186/s13046-018-0831-2.CrossRefPubMedPubMedCentral

11.

Mo Y, He L, Lai Z, Wan Z, Chen Q, Pan S, et al. LINC01287 regulates tumorigenesis and invasion via miR-298/MYB in hepatocellular carcinoma. J Cell Mol Med. 2018;22(11):5477–85. https://doi.org/10.1111/jcmm.13818.CrossRefPubMedPubMedCentral

12.

Song C, Sun P, He Q, Liu LL, Cui J, Sun LM. Long non-coding RNA LINC01287 promotes breast cancer cells proliferation and metastasis by activating Wnt/ss-catenin signaling. Eur Rev Med Pharmacol Sci. 2019;23(10):4234–42. https://doi.org/10.26355/eurrev_201905_17928.CrossRefPubMed

13.

Chu A, Liu J, Yuan Y, Gong Y. Comprehensive analysis of aberrantly expressed ceRNA network in gastric cancer with and without H.pylori infection. J Cancer. 2019;10(4):853–63. https://doi.org/10.7150/jca.27803.CrossRefPubMedPubMedCentral

14.

Cao Q, Dong Z, Liu S, An G, Yan B, Lei L. Construction of a metastasis-associated ceRNA network reveals a prognostic signature in lung cancer. Cancer Cell Int. 2020;20(1):208. https://doi.org/10.1186/s12935-020-01295-8.CrossRefPubMedPubMedCentral

15.

Chen M, Geoffroy CG, Meves JM, Narang A, Li Y, Nguyen MT, et al. Leucine zipper-bearing kinase is a critical regulator of astrocyte reactivity in the adult mammalian CNS. Cell Rep. 2018;22(13):3587–97. https://doi.org/10.1016/j.celrep.2018.02.102.CrossRefPubMedPubMedCentral

16.

Chen M, Geoffroy CG, Wong HN, Tress O, Nguyen MT, Holzman LB, et al. Leucine zipper-bearing kinase promotes axon growth in mammalian central nervous system neurons. Sci Rep. 2016;6(1):31482. https://doi.org/10.1038/srep31482.CrossRefPubMedPubMedCentral

17.

Ikeda A, Hasegawa K, Masaki M, Moriguchi T, Nishida E, Kozutsumi Y, et al. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001;130(6):773–81. https://doi.org/10.1093/oxfordjournals.jbchem.a003048.CrossRefPubMed

18.

Masaki M, Ikeda A, Shiraki E, Oka S, Kawasaki T. Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically. Eur J Biochem. 2003;270(1):76–83. https://doi.org/10.1046/j.1432-1033.2003.03363.x.CrossRefPubMed

19.

Edwards ZC, Trotter EW, Torres-Ayuso P, Chapman P, Wood HM, Nyswaner K, et al. Survival of head and neck Cancer cells relies upon LZK kinase-mediated stabilization of mutant p53. Cancer Res. 2017;77(18):4961–72. https://doi.org/10.1158/0008-5472.CAN-17-0267.CrossRefPubMed

20.

Han H, Chen Y, Cheng L, Prochownik EV, Li Y. microRNA-206 impairs c-Myc-driven cancer in a synthetic lethal manner by directly inhibiting MAP3K13. Oncotarget. 2016;7(13):16409–19. https://doi.org/10.18632/oncotarget.7653.CrossRefPubMedPubMedCentral

21.

Borowicz S, Van Scoyk M, Avasarala S, et al. The soft agar colony formation assay. J Vis Exp. 2014;92(92):e51998.

22.

Han P, Li JW, Zhang BM, Lv JC, Li YM, Gu XY, et al. The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/beta-catenin signaling. Mol Cancer. 2017;16(1):9. https://doi.org/10.1186/s12943-017-0583-1.CrossRefPubMedPubMedCentral

23.

He F, Song Z, Chen H, Chen Z, Yang P, Li W, et al. Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128. Oncogene. 2019;38(2):164–79. https://doi.org/10.1038/s41388-018-0432-8.CrossRefPubMed

24.

Yue B, Cai D, Liu C, Fang C, Yan D. Linc00152 functions as a competing endogenous RNA to confer Oxaliplatin resistance and holds prognostic values in Colon Cancer. Mol Ther. 2016;24(12):2064–77. https://doi.org/10.1038/mt.2016.180.CrossRefPubMedPubMedCentral

25.

Deng H, Wang JM, Li M, Tang R, Tang K, Su Y, et al. Long non-coding RNAs: new biomarkers for prognosis and diagnosis of colon cancer. Tumour Biol. 2017;39(6):1010428317706332. https://doi.org/10.1177/1010428317706332.CrossRefPubMed

26.

Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell. 2011;146(3):353–8. https://doi.org/10.1016/j.cell.2011.07.014.CrossRefPubMedPubMedCentral

27.

Paraskevopoulou MD, Vlachos IS, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T, et al. DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res. 2016;44(D1):D231–8. https://doi.org/10.1093/nar/gkv1270.CrossRefPubMed

28.

Peng W, Dong N, Wu S et al. miR-4500 suppresses cell proliferation and migration in bladder cancer via inhibition of STAT3/CCR7 pathway. J Cell Biochem. 2019;8(9):3913-22.

29.

Yu FY, Tu Y, Deng Y, Guo C, Ning J, Zhu Y, et al. MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2. Cancer Biol Ther. 2016;17(11):1149–57. https://doi.org/10.1080/15384047.2016.1235661.CrossRefPubMedPubMedCentral

30.

Li R, Teng X, Zhu H, Han T, Liu Q. MiR-4500 regulates PLXNC1 and inhibits papillary thyroid Cancer progression. Horm Cancer. 2019;10(4–6):150–60. https://doi.org/10.1007/s12672-019-00366-1.CrossRefPubMed

31.

Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife. 2015;4:e05005. https://doi.org/10.7554/eLife.05005.CrossRefPubMedCentral

32.

Tang X, Qiao X, Chen C, Liu Y, Zhu J, Liu J. Regulation mechanism of long noncoding RNAs in Colon Cancer development and progression. Yonsei Med J. 2019;60(4):319–25. https://doi.org/10.3349/ymj.2019.60.4.319.CrossRefPubMedPubMedCentral

33.

Weng J, Xiao J, Mi Y, Fang X, Sun Y, Li S, et al. PCDHGA9 acts as a tumor suppressor to induce tumor cell apoptosis and autophagy and inhibit the EMT process in human gastric cancer. Cell Death Dis. 2018;9(2):27. https://doi.org/10.1038/s41419-017-0189-y.CrossRefPubMedPubMedCentral

34.

Lin Q, Zheng H, Xu J et al. LncRNA SNHG16 aggravates tumorigenesis and development of hepatocellular carcinoma by sponging miR-4500 and targeting STAT3. J Cell Biochem. 2019;120(7):11604-15.

35.

Zhang L, Qian J, Qiang Y, Huang H, Wang C, Li D, et al. Down-regulation of miR-4500 promoted non-small cell lung cancer growth. Cell Physiol Biochem. 2014;34(4):1166–74. https://doi.org/10.1159/000366329.CrossRefPubMed

36.

Li ZY, Zhang ZZ, Bi H, Zhang QD, Zhang SJ, Zhou L, et al. MicroRNA4500 suppresses tumor progression in nonsmall cell lung cancer by regulating STAT3. Mol Med Rep. 2019;20(6):4973–83. https://doi.org/10.3892/mmr.2019.10737.CrossRefPubMedPubMedCentral

37.

Li S, Mai H, Zhu Y, Li G, Sun J, Li G, et al. MicroRNA-4500 inhibits migration, invasion, and angiogenesis of breast Cancer cells via RRM2-dependent MAPK signaling pathway. Mol Ther Nucleic Acids. 2020;21:278–89. https://doi.org/10.1016/j.omtn.2020.04.018.CrossRefPubMedPubMedCentral

38.

Li ZW, Xue M, Zhu BX, Yue CL, Chen M, Qin HH. microRNA-4500 inhibits human glioma cell progression by targeting IGF2BP1. Biochem Biophys Res Commun. 2019;513(4):800–6. https://doi.org/10.1016/j.bbrc.2019.04.058.CrossRefPubMed

39.

Kim K, Shin EA, Jung JH et al. Ursolic Acid Induces Apoptosis in Colorectal Cancer Cells Partially via Upregulation of MicroRNA-4500 and Inhibition of JAK2/STAT3 Phosphorylation. Int J Mol Sci. 2018;20(1):114.

40.

Zhang Q, Li X, Cui K, Liu C, Wu M, Prochownik EV, et al. The MAP3K13-TRIM25-FBXW7alpha axis affects c-Myc protein stability and tumor development. Cell Death Differ. 2020;27(2):420–33. https://doi.org/10.1038/s41418-019-0363-0.CrossRefPubMed

41.

Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer. 2013;12(1):86. https://doi.org/10.1186/1476-4598-12-86.CrossRefPubMedPubMedCentral

42.

Feng M, Feng J, Chen W, Wang W, Wu X, Zhang J, et al. Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-kappaB-dependent activation of snail and epithelial mesenchymal transition. Mol Cancer. 2016;15(1):77. https://doi.org/10.1186/s12943-016-0564-9.CrossRefPubMedPubMedCentral

43.

Pires BR, Mencalha AL, Ferreira GM, et al. NF-kappaB is involved in the regulation of EMT genes in breast Cancer cells. PLoS One. 2017;12(1):e0169622. https://doi.org/10.1371/journal.pone.0169622.CrossRefPubMedPubMedCentral

Title: LINC01287 facilitates proliferation, migration, invasion and EMT of colon cancer cells via miR-4500/MAP3K13 pathway
Authors: Dazhi Fu
Yongjun Ren
Chunxiao Wang
Lei Yu
Rui Yu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Colon Cancer
Colon Cancer
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08528-7

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