Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (10): 59-69.doi: 10.6040/j.issn.1671-7554.0.2021.0367

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Expression profiles of long non-coding RNA LINC02474 and effects on cell proliferation in colorectal cancer

DU Tiantian1,2, LI Juan1,2, ZHAO Yinghui1,2, DUAN Weili1,2, WANG Jing1,2, WANG Yunshan1,2, DU Lutao1,2, WANG Chuanxin1,2   

  1. 1. Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong, China;
    2. Tumor Marker Detection Engineering Laboratory of Shandong Provine, Jinan 250033, Shandong, China
  • Published:2021-10-15

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Abstract: Objective To explore the expression profiles of long non-coding RNA LINC02474 in tissues and circulating exosomes of colorectal cancer(CRC)and the effects of LINC02474 on cell proliferation. Methods The relative expression of LINC02474 in tissues of 30 CRC patients and serum samples from 128 CRC patients and 128 healthy donors by quantitative real-time PCR(qRT-PCR)was obtained. Morphology of the exosomes was detected by electron microscope. The size was analyzed by nanoparticle tracking analysis(NTA). Expression of exosomes markers were shown by Western blotting. The DLD-1 cell proliferation after deletion of LINC02474 was screened by CCK-8 assays, colony formation assays and the real-time cell analysis(RTCA)system. And the potential target genes were acquired by bioinformatics prediction. Results TCGA analysis and qRT-PCR results from tissues of 30 CRC patients and serum samples from 128 CRC patients and 128 healthy donors have shown that LINC02474 was highly expressed in CRC tissues samples(U=213.0, P<0.001). Morphology of the exosomes was disk-like vesicles which detected by electron microscope. The size of the exosomes mainly enriched in 96.9 nm which was analyzed by NTA. CD9, CD63 and TSG101 were expressed in the surface of the exosomes which shown by Western blotting. Deletion of LINC02474 inhibited proliferation of CRC cells, which detected by CCK-8 assays, colony formation assays and the RTCA system(CCK-8 assays: t=2.640, P=0.046;colony formation assays: t=2.745, P=0.016; RTCA system: t=28.44, P<0.001). And there were more target genes enriched in the mTOR and MAPK signaling pathway through KEGG and GO analysis. Conclusion LINC02474 is highly expressed in CRC tissues and serum samples, and its knockdown restrains the cell proliferation.

Key words: Colorectal cancer, Long non-coding RNAs, Exosomes, Diagnosis, Cell proliferation

CLC Number: 

  • R735-7
[1] Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164.
[2] Willauer AN, Liu Y, Pereira AAL, et al. Clinical and molecular characterization of early-onset colorectal cancer[J]. Cancer, 2019, 125(12): 2002-2010.
[3] Steffen P, Li J, Chandra J, et al. Molecular features of lymph node metastasis in T1/2 colorectal cancer from formalin-fixed paraffin-embedded archival specimens[J]. J Proteome Res, 2021, 20(2): 1304-1312.
[4] Burnett-Hartman AN, Lee JK, Demb J, et al. An update on the epidemiology, molecular characterization, diagnosis, and screening strategies for early-onset colorectal cancer[J]. Gastroenterology, 2021, 160(4): 1041-1049.
[5] Meng N, Chen M, Chen D, et al. Small protein hidden in lncRNA LOC90024 promotes "cancerous" RNA splicing and tumorigenesis[J]. Adv Sci(Weinh), 2020, 7(10): 1903233. doi: 1903210.1901002/advs.201903233.
[6] Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs[J]. Cell, 2009, 136(4): 629-641.
[7] Shi X, Sun M, Liu H, et al. Long non-coding RNAs: a new frontier in the study of human diseases[J]. Cancer Lett, 2013, 339(2): 159-166.
[8] Tachiwana H, Saitoh N. Nuclear long non-coding RNAs as epigenetic regulators in cancer[J]. Curr Med Chem, 2021, 28(25):5098-5109.
[9] Hu A, Hong F, Li D, et al. Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression[J]. J Transl Med, 2021, 19(1): 95. doi: 10.1186/s12967-12020-02682-12965.
[10] Melixetian M, Bossi D, Mihailovich M, et al. Long non-coding RNA TINCR suppresses metastatic melanoma dissemination by preventing ATF4 translation[J]. EMBO Rep, 2021, 22(3): e50852. doi: 50810.15252/embr.202050852.
[11] Nam GH, Choi Y, Kim GB, et al. Emerging prospects of exosomes for cancer treatment: from conventional therapy to immunotherapy[J]. Adv Mater, 2020, 32(51): e2002440. doi: 2002410.2001002/adma.202002440.
[12] Exosome profiling pinpoints cancer type[J]. Cancer Discov, 2020, 10(11): 1619. doi: 1610.1158/2159-8290.CD-NB2020-1083.
[13] Khomtchouk BB, Hennessy JR, Wahlestedt C. shinyheatmap: Ultra fast low memory heatmap web interface for big data genomics[J]. PLoS One, 2017, 12(5): e0176334. doi: 0176310.0171371/journal.pone.0176334.
[14] Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer-a call to action[J]. Nat Rev Clin Oncol, 2020, 18(4): 230-243.
[15] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[16] 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28.
[17] Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome[J]. Nature, 2001, 409(6822): 860-921.
[18] Statello L, Guo CJ, Chen LL, et al. Gene regulation by long non-coding RNAs and its biological functions[J]. Nat Rev Mol Cell Biol, 2021, 22(2): 96-118.
[19] Pefanis E, Wang J, Rothschild G, et al. RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity[J]. Cell, 2015, 161(4): 774-789.
[20] Qu L, Ding J, Chen C, et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA[J]. Cancer Cell, 2016, 29(5): 653-668.
[21] Xu R, Rai A, Chen M, et al. Extracellular vesicles in cancer-implications for future improvements in cancer care[J]. Nat Rev Clin Oncol, 2018, 15(10): 617-638.
[22] 常文婧, 李冬, 孙祖俊. 外泌体长链非编码RNA:肿瘤分子诊断新型标志物[J]. 国际检验医学杂志, 2020, 41: 1793-1799.
[23] Guo X, Lv X, Ru Y, et al. Circulating exosomal gastric cancer-associated long noncoding RNA1 as a biomarker for early detection and monitoring progression of gastric cancer: a multiphase study[J]. JAMA Surg, 2020, 155(7): 572-579.
[24] Lin LY, Yang L, Zeng Q, et al. Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer[J]. Mol Cancer, 2018, 17(1): 84. doi: 10.1186/s12943-12018-10834-12949.
[25] Qi P, Zhou XY, Du X. Circulating long non-coding RNAs in cancer: current status and future perspectives[J]. Mol Cancer, 2016, 15(1): 39. doi: 10.1186/s12943-12016-10524-12944.
[26] Dong L, Lin W, Qi P, et al. Circulating long RNAs in serum extracellular vesicles: their characterization and potential application as biomarkers for diagnosis of colorectal cancer[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25(7): 1158-1166.
[27] Zeng ZL, Lu JH, Wang Y, et al. The lncRNA XIST/miR-125b-2-3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer[J]. Cancer Med, 2021, 10(7): 2423-2441.
[28] Si Z, Yu L, Jing H, et al. Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis[J]. J Exp Clin Cancer Res, 2021, 40(1): 78. doi: 10.1186/s13046-13021-01882-13041.
[29] Wang X, Zhou J, Xu M, et al. A 15-lncRNA signature predicts survival and functions as a ceRNA in patients with colorectal cancer[J]. Cancer Manag Res, 2018, 10: 5799-5806. doi:10.2147/CMAR.S178732.
[30] Qian X, Li S, Yang Z, et al. The long non-coding RNA HLNC1 potentiates hepatocellular carcinoma progression via interaction with USP49[J]. J Clin Lab Anal, 2020, 34(11): e23462. doi: 23410.21002/jcla.23462.
[31] Li Y, Zeng C, Hu J, et al. Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression[J]. J Hematol Oncol, 2018, 11(1): 89. doi: 10.1186/s13045-13018-10632-13042.
[32] Peng W, Zhang C, Peng J, et al. Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression[J]. Cancer Lett, 2020, 494: 94-106. doi:10.1016/j.canlet.2020.08.036.
[33] Luo D, Li C, Wu L, et al. Advances of exosomes extraction and its mechanism in early diagnosis of lung cancer[J]. Zhongguo Fei Ai Za Zhi, 2020, 23(11): 999-1006.
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