WANG Yidan, WANG Boya, LI Lu, ZHANG Yong, CHU Feifei, WU Huili. Effects of N6-methyladenosine reading protein human antigen R on migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1[J]. Journal of Clinical Medicine in Practice, 2024, 28(7): 9-15. DOI: 10.7619/jcmp.20240233
Citation: WANG Yidan, WANG Boya, LI Lu, ZHANG Yong, CHU Feifei, WU Huili. Effects of N6-methyladenosine reading protein human antigen R on migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1[J]. Journal of Clinical Medicine in Practice, 2024, 28(7): 9-15. DOI: 10.7619/jcmp.20240233

Effects of N6-methyladenosine reading protein human antigen R on migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1

More Information
  • Received Date: January 14, 2024
  • Revised Date: February 14, 2024
  • Available Online: April 21, 2024
  • Objective 

    To investigate the effect of N6-methyladenosine (m6A) reading protein human antigen R (HuR) on the migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1 (PFK1).

    Methods 

    The tissue samples of 33 patients who were first diagnosed as colorectal cancer in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April to December 2022 were collected. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of HuR and PFK1 mRNA in colorectal cancer tissues and adjacent tissues. The expression of HuR mRNA in normal intestinal epithelial cells NCM460 and colorectal cancer cells HCT8, SW480, SW620, HCT116, LoVo, RKO and COLO205 was detected. Small interfering RNA (siRNA) was used to construct a HuR knockdown colorectal cancer cell model. The effects of HuR on the migration and invasion of colorectal cancer cells were detected by cell scratch assay and Transwell assay. The expression of PFK1 mRNA and protein was detected by qRT-PCR and Western blot. Glucose intake and pyruvate production were detected by glucose content kit and pyruvate content kit, respectively. The relationship between HuR and PFK1 was analyzed by bioinformatics analysis, and the effect of HuR on the stability of PFK1 mRNA was evaluated by actinomycin D assay.

    Results 

    In colorectal cancer tissues, HuR and PFK1 were highly expressed at mRNA level; HuR was highly expressed at mRNA level in colorectal cancer cell lines. Down-regulation of HuR significantly inhibited the migration and invasion of colorectal cancer cells, as well as glucose consumption and pyruvate production. Knockdown of HuR could reduce the stability of PFK1 mRNA and its expression at mRNA and protein levels. There were m6A modification sites on PFK1.

    Conclusion 

    The m6A reading protein HuR may regulate the migration, invasion and glycolysis of colorectal cancer cells by recognizing the m6A site on PFK1 and reducing the stability of PFK1 mRNA.

  • [1]
    XI Y, XU P F. Global colorectal cancer burden in 2020 and projections to 2040[J]. Transl Oncol, 2021, 14(10): 101174. doi: 10.1016/j.tranon.2021.101174
    [2]
    JIANG Y F, YUAN H Y, LI Z Y, et al. Global pattern and trends of colorectal cancer survival: a systematic review of population-based registration data[J]. Cancer Biol Med, 2021, 19(2): 175-186.
    [3]
    KOCIANOVA E, PIATRIKOVA V, GOLIAS T. Revisiting the Warburg effect with focus on lactate[J]. Cancers, 2022, 14(24): 6028. doi: 10.3390/cancers14246028
    [4]
    程多, 褚菲菲, 张楠, 等. 果糖二磷酸醛缩酶C在结肠癌组织和细胞中的表达及其对生物学行为的影响[J]. 实用医学杂志, 2023, 39(15): 1893-1900. doi: 10.3969/j.issn.1006-5725.2023.15.007
    [5]
    LI S, HE P, WANG Z W, et al. RNAi-mediated knockdown of PFK1 decreases the invasive capability and metastasis of nasopharyngeal carcinoma cell line, CNE-2[J]. Cell Cycle, 2021, 20(2): 154-165. doi: 10.1080/15384101.2020.1866279
    [6]
    杨相颖, 安宁, 谭耀, 等. 6-甲基腺嘌呤RNA甲基化与眼科疾病的研究进展[J]. 实用临床医药杂志, 2022, 26(13): 139-144. doi: 10.7619/jcmp.20220245
    [7]
    WANG Y M, WANG Y, PATEL H, et al. Epigenetic modification of m6A regulator proteins in cancer[J]. Mol Cancer, 2023, 22(1): 102. doi: 10.1186/s12943-023-01810-1
    [8]
    CHANG Y Z, CHAI R C, PANG B, et al. METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma[J]. Cancer Lett, 2021, 511: 36-46. doi: 10.1016/j.canlet.2021.04.020
    [9]
    LIANG Y K, WANG H, CHEN B, et al. circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression[J]. Mol Ther Nucleic Acids, 2021, 23: 355-368. doi: 10.1016/j.omtn.2020.11.012
    [10]
    QIN C T, LIU S Y, CHEN W B, et al. HuR-induced circ_0082319 contributes to hepatocellular carcinoma by elevating PTK2 through miR-505-3p[J]. Naunyn Schmiedebergs Arch Pharmacol, 2023: Online ahead of print.
    [11]
    CHEN H, ZHANG L F, MIAO Y, et al. Verteporfin suppresses YAP-induced glycolysis in breast cancer cells[J]. J Invest Surg, 2023, 36(1): 2266732. doi: 10.1080/08941939.2023.2266732
    [12]
    FANG Z, MEI W T, QU C, et al. Role of m6A writers, erasers and readers in cancer[J]. Exp Hematol Oncol, 2022, 11(1): 45. doi: 10.1186/s40164-022-00298-7
    [13]
    柴小兵, 张利, 褚菲菲, 等. m6A识别蛋白HuR调控lncRNA TRG-AS1抑制结直肠癌生长的机制研究[J]. 天津医药, 2023, 51(2): 124-131. https://www.cnki.com.cn/Article/CJFDTOTAL-TJYZ202302003.htm
    [14]
    DUAN X H, CHEN R, LI D S, et al. HuR affects chemoresistance of small cell lung cancer by regulating FGFRL1 expression[J]. Exp Ther Med, 2022, 24(4): 638. doi: 10.3892/etm.2022.11575
    [15]
    LIU H L, LAN T, LI H, et al. Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR[J]. Theranostics, 2021, 11(3): 1396-1411. doi: 10.7150/thno.53227
    [16]
    WANG J H, MAO L, WANG J, et al. Beyond metabolic waste: lysine lactylation and its potential roles in cancer progression and cell fate determination[J]. Cell Oncol, 2023, 46(3): 465-480. doi: 10.1007/s13402-023-00775-z
    [17]
    DAVERIO Z, BALCERCZYK A, RAUTUREAU G J P, et al. How warburg-associated lactic acidosis rewires cancer cell energy metabolism to resist glucose deprivation[J]. Cancers, 2023, 15(5): 1417. doi: 10.3390/cancers15051417
    [18]
    KOZAL K, JÓZWIAK P, KRZESLAK A. Contemporary perspectives on the Warburg effect inhibition in cancer therapy[J]. Cancer Control, 2021, 28: 10732748211041243.
    [19]
    FUKUSHI A, KIM H D, CHANG Y C, et al. Revisited metabolic control and reprogramming cancers by means of the Warburg effect in tumor cells[J]. Int J Mol Sci, 2022, 23(17): 10037. doi: 10.3390/ijms231710037
    [20]
    CAMPOS M, ALBRECHT L V. Hitting the sweet spot: how glucose metabolism is orchestrated in space and time by phosphofructokinase-1[J]. Cancers, 2023, 16(1): 16.
    [21]
    HU L, ZENG Z C, XIA Q, et al. Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1α/PFKFB3/PFK1 pathway[J]. Life Sci, 2019, 239: 116966.
    [22]
    LIN S, LI Y, WANG D, et al. Fascin promotes lung cancer growth and metastasis by enhancing glycolysis and PFKFB3 expression[J]. Cancer Lett, 2021(518): 230-242.
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