Abstract： Hypoxia-inducible factor-α(HIF-1α) is a regulatory protein in human body,which is closely related to the occurrence and development of cervical cancer. HIF-1α is an important factor affecting the radiosensitivity of cervical cancer. Many genes and proteins are involved in the regulation of radiosensitivity by HIF-1α. These genes and proteins are directly or indirectly affecting the efficacy of radiotherapy for cervical cancer. A lot of research is under way. This review summarizes the recent advances in genes and proteins associated with HIF-1α affecting radiosensitivity in cervical cancer.
Hu Quhui,Han Li,He Xiao et al. Progresses in research of hypoxia inducible factor-1α in radiosensitivity of cervical cancer[J]. Chinese Journal of Radiation Oncology, 2019, 28(8): 630-633.
[1] Siegel R,Jiemin M,Zou ZH,et al. Cancer statistics,2014[J]. Ca A Cancer J Clin,2014,64(1):9-29. DOI:10.3322/caac.21208. [2] Iia B,Gorbunova VA,Kravets OA,et al. Chemoradiotherapy for locally advanced cervical cancer[J]. Vopr Onkol,2014,60(3):280-287. [3] Semenza GL. Hydroxylation of HIF-1:oxygen sensing at the molecular l evel[J]. Physiology,2004,19(4):176-182. DOI:10.1152/physiol.00001.2004. [4] Chandel NS,Budinger G R S. The cellular basis for diverse responses to oxygen[J]. Free Radic Biol Med,2007,42(2):165-174. DOI:10.1016/j.freeradbiomed.2006.10.048. [5] Wang GL,Jiang BH,Rue EA,et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension[J]. Proc Nat Acad Sci USA,1995,92(12):5510-5514. [6] Wang GL,Semenza GL. Purification and characterization of hypoxia-inducible factor 1[J]. J Biolog Chem,1995,270. DOI:10.1074/jbc.270.3.1230. [7] Yang LI,Jun-Xia W,Ting G. Expression and clinical significance of hypoxia inducible factor-1 alpha in cervical carcinoma[J]. Mili Med J South China,2014,28(2):142-145. DOI:10.3969/j.issn.1009-2595.2014.02.018. [8] Yang-Yang L,Peng K,Qin XU,et al. The expression and clinical significance of HIF-1α,twist and MDR1 gene in advanced cervical cancer[J]. J Kunming Med Univ,2015,36(7):54-57. DOI:10.3969/j.issn.1003-4706.2015.07.012. [9] Tao JH,Barbi J,Pan F. Hypoxia-inducible factors in T lymphocyte differentiation and function. A review in the theme:cellular responses to hypoxia[J]. Am J Physiol Cell Physiol,2016,309(9):C580. DOI:10.1152/ajpcell.00204.2015. [10] Daido S. Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy[J]. Cancer Res,2005,65(10):4368-4375. DOI:10.1158/0008-5472. CAN-04-4202. [11] Sakata KI,Someya M,Matsumoto Y,et al. Ability to repair DNA double-strand breaks related to cancer susceptibility and radiosensitivity[J]. Radiat Med,2007,25(9):433-438. DOI:10.1007/s11604-007-0161-3. [12] Seong J. Challenge and hope in radiotherapy of hepatocellular carcinoma[J]. Yonsei Med J,2009,50(5):601-612. DOI:10.3349/ymj.2009.50.5.601. [13] Xu P,Zhu P,Ou Y,et al. Expression of VEGF and HIF-Iα in locally advanced cervical cancer:potential biomarkers for predicting preoperative radiochemotherapy sensitivity and prognosis[J]. Oncotarg Ther,2016,9(1):3031-3037. DOI:10.2147/OTT. S104142. [14] Liu LX,Lu H,Luo Y,et al. Stabilization of Vascular Endothelial Growth Factor mRNA by Hypoxia-Inducible Factor 1[J]. Biochem Biophys Res Commun,2002,291(4):0-914. DOI:10.1006/bbrc.2002.6551. [15] Abell AN,Johnson GL. Implications of mesenchymal cells in cancer stem cell populations:relevance to EMT[J]. Cur Pathobiol Rep,2014,2(1):21-26. DOI:10.1007/s40139-013-0034-7 [16] 王立峰. 一种新的低氧应激反应基因NDRG2的确定及其功能的初步研究[D].西安:第四军医大学,2006. Wang LF. Identification of a novel hypoxia-inducible gene NDRG2 and its primary founction studies[D]. Xi′an:The fourth military medical university,2006. [17] Liu J,Zhang J,Wang X,et al. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer hela cells[J]. Exper Cell Res,2010,316(12):1985-1993. DOI:10.1016/j.yexcr.2010.02.028. [18] Xiang L,Gilkes DM,Hu H,et al. HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells[J]. Oncotarget,2015,6(14):11768-11778. DOI:10.1111/j.1445-2197.2010.05546.x. [19] 向丽莎. HIF-1α调控TAZ和GLS2对维持肿瘤干细胞表型及介导肿瘤放疗耐受的机制研究[D].重庆:第三军医大学,2015. Xiang LS. HIF-1α regulates cancer stem cell phenotype and radioresistance through HIF-dependent-TAZ and-GLS2 pathway in cancer cells[D]. Chongqing:Third military medical university,2015. [20] 白帆. TAZ和Lats2在食管鳞癌组织的表达及临床意义[D].广州:第二军医大学,2017. Bai F. Expression and clinical significance of TAZ and Lasts2 in Esophageal squamous cell carcinoma[D]. Guangzhou:The scond military medical university,2017. [21] Song L,Liu S,Zhang L,et al. MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1α feedback loop and the Akt-mTOR signaling pathway[J]. Tumor Biol,2016,37(9):12161-12168. DOI:10.1007/s13277-016-5073-3. [22] Liu S,Song L,Zhang L,et al.miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1[J]. Biochem Biophys Res Commun,2015,459(4):679-685. DOI:10.1016/j.bbrc.2015.03.004. [23] 李云,暴金玲,尹国武. 宫颈癌组织中HIF-α、p53及Beclin1的表达水平探讨[J]. 中国妇幼健康研究, 2018(2):181-184. DOI:10.3969/j.issn.1673-5293.2018.02.013. Li Y,BaoJL,Yin GW. Expression levels of HIF-α,p53 and Belicn1 in cervical cancer tissue[J]. Chin J Woman Child Heal Res,2018(2):181-184. DOI:10.3969/j.issn.1673-5293.2018.02.013. [24] Fu Z,Chen D,Cheng H,et al. Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia[J]. Int Med J Exper Clin Res,2015,21(42):318-325. DOI:10.12659/MSM.893265. [25] Ganhong C,Pathology DO. The expression of TLR4 in cervical cancer and its relationship with HIF-1α[J]. Pract J Cancer,2013,28(6):608-610. DOI:10.3969/j.issn.1001-5930,2013.06.009. [26] Yang X,Chen GT,Wang YQ,et al. TLR4 promotes the expression of HIF-1α by triggering reactive oxygen species in cervical cancer cells in vitro-implications for therapeutic intervention[J]. Mol Med Rep,2018,17(2):2229-2238. DOI:10.3892/mmr.2017.8108. [27] 杨菁. 胃癌细胞中KLF4基因的表达及KLF4基因启动子区的生物信息学分析[D].贵阳:贵阳医学院,2015. Yang J. Expression of KLF4 gene in gastric cancer cells and bioinformatics analysis on promoter region of KLF4 gene[D]. Guiyang:Guiyang medical college,2015. [28] 刘海霞. KLF4抑制宫颈癌放射敏感性及其分子机制研究[D].西安:第四军医大学,2017. Liu HX. Inhibitory effect of KLF4 on radiosensitivity of cervical cancer and its molecular mechanism[D]. Xi′an:The fourth military medical university,2017. [29] 刘邦. Eag1钾通道在子宫颈癌中的表达及其阻断剂的放疗增敏作用[D].南充:川北医学院,2013. Liu B. Expression of eag1 potassium channel uterine cercical cancer and radiotherapys sensitization for its bloker[D]. Nanchong:North sichuan medical college,2013. [30] Bullen JW,Tchernyshyov I,Holewinski RJ,et al. Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1[J]. Sci Sig,2016,9(1):ra56-ra56. DOI:10.1126/scisignal.aaf0583.
2019, Vol. 28 
