Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (10): 103-109.doi: 10.6040/j.issn.1671-7554.0.2018.590

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Effect of IQ motif-containing GTPase activating protein 3 on the proliferation and migration of cervical cancer cells

WANG Yong1, JIANG Chen2, ZHOU Shiying1, YANG Xiaomei3   

  1. 1. Department of Obstetrics, Jinan Maternity and Child Care Hospital, Jinan 250002, Shandong, China;
    2. Department of Gynaecology, Jinan Maternity and Child Care Hospital, Jinan 250002, Shandong, China;
    3. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2018-05-20 Published:2022-09-27

Abstract: Objective To investigate the expression of IQ motif-containing GTPase activating protein 3(IQGAP3)in the cervical cancer tissues and cell lines, and its subsequent influences on cell proliferation, apoptosis and migration. Methods The expression of IQGAP3 was analyzed by immunohistochemistry and real-time PCR in cervical cancer and adjacent normal tissues. The siRNA targeting IQGAP3 was used to knockdown the expression of IQGAP3. The influences of IQGAP3 silencing on cancer cell proliferation, apoptosis and migration were determined by MTT methods, flow cytometry and transwell migration assay, respectively. Results The expression of IQGAP3 was up-regulated in the cervical cancer tissues and cervical cancer cell lines. The up-regulation of IQGAP3 was associated with the poor prognosis of patients with cervical cancer(χ2=6.15, P=0.01). Down-regulation of IQGAP3 decreased proliferation and promoted apoptosis in CaSki and HeLa cells. Moreover, as compared with siScramble transfected cells, the number of migrating cell was significantly decreased in CaSki and HeLa cells due to si-IQGAP3 transfection. In addition, Western blotting analysis showed that knockdown of IQGAP3 increased the expression of epithelial marker E-cadherin and decreased the 山 东 大 学 学 报 (医 学 版)56卷10期 -王永,等.IQ结构域GTP酶激活蛋白3表达对宫颈癌细胞增殖和转移的影响 \=-expression of mesenchymal marker N-cadherin(all P<0.001). Conclusion IQGAP3 is up-regulated in cervical cancer tissues and cells, and its ver-expression promots cell proliferation and the migration capacity in cervical cancer cells. IQGAP3 plays a key role in cervical cancer progression and could be a potential therapeutic target for cervical cancer.

Key words: IQ motif-containing GTPase activating protein 3, Cervical cancer, Cell proliferation, Cell apoptosis, Epithelial-mesenchymal transition

CLC Number: 

  • R737.33
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[2] Minion LE, Tewari KS. Cervical cancer—state of the science: from angiogenesis blockade to checkpoint inhibition[J]. Gynecol Oncol, 2018, 148(3): 609-621.
[3] 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. doi: 10.3322/caac.21492.
[4] Erickson JW, Cerione RA, Hart MJ. Identification of an actin cytoskeletal complex that includes IQGAP and the Cdc42 GTPase[J]. J Biol Chem, 1997, 272(39): 24443-24447.
[5] Hedman AC, Smith JM, Sacks DB. The biology of IQGAP proteins: beyond the cytoskeleton[J]. EMBO Rep, 2015, 16(4): 427-446.
[6] Wang S, Watanabe T, Noritake J, et al. IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth[J]. J Cell Sci, 2007, 120(Pt 4): 567-577.
[7] Smith JM, Hedman AC, Sacks DB. IQGAPs choreograph cellular signaling from the membrane to the nucleus[J]. Trends Cell Biol, 2015, 25(3): 171-184.
[8] Hu G, Xu Y, Chen W, et al. RNA interference of IQ motif containing GTPase-activating protein 3(IQGAP3)inhibits cell proliferation and invasion in breast carcinoma cells[J]. Oncol Res, 2016, 24(6): 455-461.
[9] Pathmanathan S, Hamilton E, Atcheson E, et al. The interaction of IQGAPs with calmodulin-like proteins[J]. Biochem Soc Trans, 2011, 39(2): 694-699.
[10] Skawran B, Steinemann D, Weigmann A, et al. Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions[J]. Mod Pathol, 2008, 21(5):505-516.
[11] Shi Y, Qin N, Zhou Q, et al. Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma[J]. J Transl Med, 2017, 15(1): 176. doi: 10.1186/s12967-017-1275-8.
[12] Yang Y, Zhao W, Xu QW, et al. IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells[J]. PLoS One, 2014, 9(5): e97578. doi: 10.1371/journal.pone.0097578.
[13] Doubeni CA, Gabler NB, Wheeler CM, et al. Timely follow-up of positive cancer screening results: a systematic review and recommendations from the PROSPR Consortium[J]. CA Cancer J Clin, 2018, 68(3): 199-216.
[14] Bao HL, Wang LH, Wang LM, et al. [Study on the coverage of cervical and breast cancer screening among women aged 35-69 years and related impact of socioeconomic factors in China, 2013] [J]. Zhonghua Liu Xing Bing Xue Za Zhi, 2018, 39(2): 208-212.
[15] Hart MJ, Callow MG, Souza B, et al. IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs[J]. EMBO J, 1996, 15(12): 2997-3005.
[16] Kim WT, Kim YH, Jeong P, et al. Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer[J]. Oncotarget, 2018, 9(18): 14354-14365.
[17] Oue N, Yamamoto Y, Oshima T, et al. Overexpression of the transmembrane protein IQGAP3 is associated with poor survival of patients with gastric cancer[J]. Pathobiology, 2018, 85(3): 192-200.
[18] Fang X, Zhang B, Thisse B, et al. IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development[J]. Cytoskeleton(Hoboken), 2015, 72(8): 422-433.
[19] Wu K, Zhang X, Li F, et al. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas[J]. Nat Commun, 2015, 6: 10131. doi: 10.1038/ncomms10131.
[20] Xu W, Xu B, Yao Y, et al. Overexpression and biological function of IQGAP3 in human pancreatic cancer[J]. Am J Transl Res, 2016, 8(12): 5421-5432.
[21] Nojima H, Adachi M, Matsui T, et al. IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade[J]. Nat Cell Biol, 2008, 10(8): 971-978.
[22] Zhou Z, Li W, Zhang F, et al. The value of squamous cell carcinoma antigen(SCCa)to determine the lymph nodal metastasis in cervical cancer: a meta-analysis and literature review[J]. PLoS One, 2017, 12(12): e0186165. doi: 10.1371/journal.pone.0186165.
[23] Qureshi R, Arora H, Rizvi MA. EMT in cervical cancer: its role in tumour progression and response to therapy[J]. Cancer Lett, 2015, 356(2 Pt B): 321-331.
[24] Yuan Y, Ye HQ, Ren QC. Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition, as well as the migration and invasion of cervical cancer[J]. Int J Oncol, 2018, 52(2): 461-472.
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