Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (3): 67-73.doi: 10.6040/j.issn.1671-7554.0.2020.1734

Previous Articles    

Relationship between methylation of tumor suppressor genes SOCS1 and SOCS3 and remission and prognosis of 80 acute myeloid leukemia patients

ZHANG Xiaohui1, LUO Jianmin2, SUO Xiaohui1, SUN Guofeng1, LI Jing3   

  1. 1. Department of Hematology, Handan Central Hospital, Handan 056001, Hebei, China;
    2. Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China;
    3. Department of Oncology, Handan Central Hospital, Handan 056001, Hebei, China
  • Published:2021-04-06

Abstract: Objective To explore the relationship between SOCS1 and SOCS3 methylation, remission and prognosis of acute myeloid leukemia(AML). Methods The methylation and expressions of SOCS1 and SOCS3 in 80 AML patients and 20 healthy controls were detected with RT-qPCR, MS-PCR and Western blotting. The chromosome karyotypes were determined with R+G banding method. The AML group was subdivided into SOCS1 methylation group(n=39)and SOCS1 non-methylation group(n=41), SOCS3 methylation group(n=44)and SOCS3 non-methylation group(n=36). The age, sex and AML typing were compared. The gene mutation, karyotypes, complete remission rate and AML prognosis stages were compared among the two-gene methylation group(n=29), single-gene methylation group(n=25)and double-unmethylation group(n=26). Results The AML group had higher methylation rates of SOCS1 and SOCS3 genes than the control group(48.75% vs 0, 55% vs 0), and the mRNA expressions were lower [SOCS1: 0.080(0.003, 1.090)vs 1.677(0.422, 1.972); SOCS3: 0.140(0.002, 1.044)vs 2.395±1.540](P<0.001). In AML patients, the mRNA and protein expressions of SOCS1 and SOCS3 methylation groups were lower than those in non-methylation groups and control group(P<0.001). The positive rate of WT1/ABL in SOCS1 and SOCS3 methylation groups was higher than that in non-methylation groups(χ2=9.674, P=0.008). The SOCS1 and SOCS3 methylation groups had a lower therapy remission rate than the non-methylation groups(χ2=10.583, P=0.005). Analysis of gene methylation and prognosis revealed that methylation of SOCS1 and SOCS3 was correlated with poor molecular abnormalities(χ2=6.137, P=0.046). Double unmethylation of SOCS1 and SOCS3 was correlated with good cytogenetics(χ2=6.675, P=0.036)and molecular abnormalities(χ2=9.693, P=0.008)of AML. Conclusion Methylation of SOCS1 and SOCS3 genes can cause gene silencing, which is associated with poor remission and prognosis of AML.

Key words: SOCS1 gene, SOCS3 gene, Acute myeloid leukemia, Methylation, WT1/ABL gene, FLT3-ITD gene

CLC Number: 

  • R552
[1] Ghazawi FM, Le M, Cyr J, et al. Analysis of acute myeloid leukemia incidence and geographic distribution in Canada from 1992 to 2010 reveals disease clusters in Sarnia and other industrial US border cities in Ontario [J]. Cancer, 2019, 125(11): 1886-1897.
[2] Takami A. Hematopoietic stem cell transplantation for acute myeloid leukemia [J]. Int J Hematol, 2018, 107(5): 513-518.
[3] Orla CO, Gargan S, Michelle KM, et al. The hepatitis C virus(HCV)protein, p7, suppresses inflammatory responses to tumor necrosis factor(TNF)-α via signal transducer and activator of transcription(STAT)3 and extracellular signal-regulated kinase(ERK)-mediated induction of suppressor of cytokine signaling(SOCS)3 [J]. FASEB J, 2019, 33(8): 8732-8744.
[4] Liu KK, Wu ZY, Chu JH, et al. Promoter methylation and expression of SOCS3 affect the clinical outcome of pediatric acute lymphoblastic leukemia by JAK/STAT pathway [J]. Biomed Pharmacother, 2019, 115(7): 108913. doi: 10.1016/j.biopha.2019.108913.
[5] Shao N, Ma G, Zhang JY, et al. miR-221-5p enhances cell proliferation and metastasis through post-transcriptional regulation of SOCS1 in human prostate cancer [J]. BMC Urology, 2018, 18(1): 14. doi: 10.1186/s12894-018-0325-8.
[6] Khan MGM, Ghosh A, Variya B, et al. Hepatocyte growth control by SOCS1 and SOCS3 [J]. Cytokine, 2019, 9(121): 154733. doi: 10.1016/j.cyto.2019.154733.
[7] Liau NPD, Laktyushin A, Lucet IS, et al. The molecular basis of JAK/STAT inhibition by SOCS1 [J]. Nat Commun, 2018, 9(1): 1558. doi: 10.1038/s41467-018-04013-1.
[8] Feng RY, Wang XF, Li JN, et al. Interaction of Abl tyrosine kinases with SOCS3 impairs its suppressor function in tumorigenesis [J]. Neoplasia, 2018, 20(11): 1095-1105.
[9] Wang YM, Lu C, Huang HX, et al. A lipid-soluble extract of pinellia pedatisecta schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer [J]. J Ethnopharmacology, 2021, 267(3): 112837. doi: 10.1016/j.jep.2020.112837.
[10] Karki P, Ke YB, Zhang CO, et al. SOCS3-microtubule interaction via CLIP-170 and CLASP is critical for modulation of endothelial inflammation and lung injury [J]. J Biol Chem, 2020, 120(12): 14232. doi: 10.1074/jbc.RA120.014232.
[11] Ying J, Qiu XY, Lu Y, et al. SOCS1 and its potential clinical role in tumor [J]. Pathol Oncol Res, 2019, 25(4): 1295-1301.
[12] Khan MGM, Ghosh A, Variya B, et al. Prognostic significance of SOCS1 and SOCS3 tumor suppressors and oncogenic signaling pathway genes in hepatocellular carcinoma [J]. BMC Cancer, 2020, 20(1): 774. doi: 10.1186/s12885-020-07285-3.
[13] Gong Y, Wan JH, Zou W, et al. MiR-29a inhibits invasion and metastasis of cervical cancer via modulating methylation of tumor suppressor SOCS1 [J]. Future Oncol, 2019, 15(15): 1729-1744.
[14] Pasha HF, Mohamed RH, Radwan MI. RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma [J]. Cancer Biomark, 2019, 24(2): 241-247.
[15] 冼海兵, 冯卫能, 张华, 等. miR-155与SOCS1在非小细胞肺癌中表达及临床意义[J]. 肿瘤学杂志, 2020, 26(7):586-590. XI Haibing, FENG Weineng, ZHANG Hua, et al. Expression of miR-155 and SOCS-1 in non-small cell lung cancer and its clinical significance [J]. Journal of Oncology, 2020, 26(7): 586-590.
[16] Villalobos-Hernandez A, Bobbala D, Kandhi R, et al. SOCS1 inhibits migration and invasion of prostate cancer cells, attenuates tumor growth and modulates the tumor stroma [J]. Prostate Cancer Prostatic Dis, 2017, 20(1): 36-47.
[17] Zhao R, Chen K, Zhou J, et al. The prognostic role of BORIS and SOCS3 in human hepatocellular carcinoma [J]. Medicine(Baltimore), 2017, 96(12): e6420. doi: 10.1097/MD.0000000000006420.
[18] Jiang MM, Zhang WW, Zhang R, et al. Cancer exosome-derived miR-9 and miR-181a promote the development of early-stage MDSCs via interfering with SOCS3 and PIAS3 respectively in breast cancer [J]. Oncogene, 2020, 39(24): 4681-4694.
[19] Li MZ, Lai DH, Zhao HB, et al. SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells [J]. Eur Rev Med Pharmacol Sci, 2017, 21(13): 3005-3011.
[20] Yoneda T, Kunimura N, Kitagawa K, et al. Overexpression of SOCS3 mediated by adenovirus vector in mouse and human castration-resistant prostate cancer cells increases the sensitivity to NK cells in vitro and in vivo [J]. Cancer Gene Therapy, 2019, 26(11): 388-399.
[21] Zhang XH, Yang L, Liu XJ, et al. Association between methylation of tumor suppressor gene SOCS1 and acute myeloid leukemia [J]. Oncol Rep, 2018, 40(2): 1008-1016.
[22] 张晓慧, 罗建民, 索晓慧, 等. SOCS1的表观遗传学修饰与急性髓系白血病的关系[J]. 中国癌症杂志, 2020, 30(8): 577-585. ZHANG Xiaohui, LUO Jianmin, SUO Xiaohui, et al. Relationship between epigenetic modification of SOCS1 and acute myeloid leukemia [J]. China Oncology, 2020, 30(8): 577-585.
[23] Chu QJ, Shen D, He L, et al. Prognostic significance of SOCS3 and its biological function in colorectal cancer [J]. Gene, 2017, 627(9): 114-122.
[1] CHEN Qi, LI Jiaqi, GUO Zhibin, JIA Jingyu, HE Linsheng. Role of methylation status of the cyclooxygenase-2 gene promoter in endometriosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 44-48.
[2] ZHOU Xue, WANG Yanrong, TIAN Long, MA Lianghong, YAN Bei, TIAN Jia, ZHANG Fan, ZHOU Yue, WANG Hongyan. DNA methylation and expression of SNRPN and GRB10 imprinted genes in human semen freezing-thawing process [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 54-59.
[3] YANG Juan, QIU Zongjian, SONG Qiang. Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(6): 28-32.
[4] REN Hongbo, LIU Hainan, LIU Cheng, YAN Keqiang, XIA Chuanyou, FAN Yidong. Clinical significance of human telomerase reverse transcriptase gene methylation status in urine sediments of renal cell carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(1): 73-76.
[5] LI Hongli, WANG Yan, XU Wenwei, DONG Lin, GUO Yan, ZHU Chuansheng, BI Kehong. Changes of NF-κB expression after promoter demethylation of TMS1 in K562 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 62-66.
[6] FAN Hai-yan, ZHANG Hui-jing, GUO Zhan-jun, LI Sheng-mian. Prognostic significance of RASSF1A and WIF-1 methylation in the cancer tissues of patients with HCC [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(5): 89-93.
[7] HOU Bei-bei, WANG Yan, ZHANG Juan, LIANG Xiao-hui, LI Jin-song. Clinicopathological significances of WIF-1 gene methylation and Wnt-5a protein expression in chondrosarcoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 70-74.
[8] XU Jia, SONG Qiang. Deletion of the RASSF1A gene and promoter methylation in the bone marrow of patients with myelodysplastic syndromes [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 65-69.
[9] CHEN Hai-yan, YAO Shu-zhe, ZHANG Xiao-ying, ZHANG Jian-ping, ZHANG Cui-juan, ZHANG Ting-guo. Effect of the methylation of SOCS-3 and 3-OST-2 genes in endometrial cancer and its clinical pathological significances [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(06): 75-80.
[10] ZHU Xun-xun1, ZHU Chuan-sheng2, WANG Yan2, XU Wen-wei2, DONG Lin2, GUO Yan2, LI Hong-li1, BI Ke-hong2 . Analysis of methylation of the Dickkopf1 (DKK1) gene in acute leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(5): 84-.
[11] YIN Dong-mei1, XU Hong-zhi1, ZHANG Jing-yao1, SUI Xiao-hui1, CUI Bin2, MA Chun-yan2, ZHEN Chang-qing1. Changes and clinical significances of CD4+T cell subsets in aplastic anemia,
myelodysplastic syndromes and acute myeloid leukemia patients
[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(3): 66-70.
[12] GUO Xiao-yu1, JIANG Yan2, XING Zhao-quan3, GUO Zhao-xin3, FANG Zhi-qing3, LIU Zhao-xu1,3. The effect of methyltransferase inhibitor on the expression of
XAF1 mRNA in prostate cancer
[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(12): 94-.
[13] KONG Hai-li, MA Dao-xin, ZHANG Jingjing, WANG Hui-jun, LIU Chuan-fang. Expression and significance of PDCD4 and TGF-β1 in patients with acute myeloid leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(6): 110-114.
[14] XU Xin, DAI Qiuxin, XU Maozhong, ZHAO Yu, MENG Wenjun . Decitabine induces demethylation and up-regulates transcription of the P15INK4B gene in lymphoma cell line Raji cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(7): 61-.
[15] LU Fei, LIU Chuanfang, MA Daoxin, LIU Yanping,KONG Haili, ZHANG Jingjing. Effect of 5-Aza-2′-deoxycytidine on SOCS-1 gene expression, proliferation and apoptosis in RPMI8226 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(4): 45-.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!