Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (7): 12-18.doi: 10.6040/j.issn.1671-7554.0.2022.1290

• 基础医学 • Previous Articles     Next Articles

Expressions and clinical significance of DEC2 and HIF-2α in gastric cancer

FAN Rong1, LI Binbin1,2, MA Xiaoli1, WANG Yunshan1, JIA Yanfei1   

  1. 1. Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan 250013, Shandong, China;
    2. Central Laboratory, Weihai Municipal Hospital, Weihai 264299, Shandong, China
  • Published:2023-07-04

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Abstract: Objective To investigate the expressions of differentiated embryonic chondrocyte gene 2(DEC2)and hypoxia inducible factor-2α(HIF-2α)and their relationship with the clinicopathological parameters of gastric cancer. Methods The gastric cancer cell lines MKN45 and HGC27 were divided into the experimental groups(hypoxia for 72 hours)and the control group(normoxic for 72 hours). The mRNA and protein expressions of DEC2 and HIF-2α were detected. The overexpression plasmid DEC2 was transfected into the cell lines to detect the protein expressions of DEC2 and HIF-2α. The expressions of DEC2 and HIF-2α in 60 cases of gastric cancer tissues and corresponding adjacent gastric mucosa tissues were detected with immunohistochemical staining, and their correlation was analyzed. Results After hypoxia treatment, the mRNA and protein expressions of DEC2 were significantly decreased in the experimental groups compared with the control groups, while the expressions of HIF-2α were increased. After overexpression of DEC2, the expression of HIF-2α decreased. The expression of DEC2 in gastric cancer tissues was significantly lower than that in adjacent gastric mucosa tissues(χ2=20.512, P<0.001), while the expression of HIF-2α was higher(χ2=11.172, P=0.001). The expressions of DEC2 and HIF-2α were significantly correlated with the depth of tumor invasion, lymph node metastasis and clinical stage, and the expressions of DEC2 and HIF-2α were negatively correlated with each other(P<0.001). Conclusion DEC2 is lowly expressed in gastric cancer cells and tissues, while HIF-2α is highly expressed. They are negatively correlated with other and closely related with the tumor development and metastasis.

Key words: Gastric cancer, Differentiated embryonic chondrocyte gene 2, Hypoxia inducible factor-2α, Hypoxia, Immunohistochemistry

CLC Number: 

  • R735.2
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Thrift AP, El-Serag HB. Burden of gastric cancer [J]. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542.
[3] Roy S, Kumaravel S, Sharma A, et al. Hypoxic tumor microenvironment: implications for cancer therapy [J]. Exp Biol Med(Maywood), 2020, 245(13): 1073-1086.
[4] 牟宏芳, 赵以览, 张晓静, 等. 缺氧及缺氧诱导因子对不同器官相关疾病调控的研究进展 [J]. 兰州大学学报(医学版), 2022, 48(5): 72-78. MOU Hongfang, ZHAO Yilan, ZHANG Xiaojing, et al. Research progress in the regulation of hypoxia and hypoxia-inducible factors in different organ-related diseases [J]. Journal of Lanzhou University(Medical Sciences), 2022, 48(5): 72-78.
[5] 曹悦悦, 吴雪琼, 赵思文, 等. 转录调节因子DEC2和肿瘤的研究进展[J]. 现代肿瘤医学, 2015, 23(7): 1002-1004. CAO Yueyue, WU Xueqiong, ZHAO Siwen, et al. A review of a transcriptional regulation factor DEC2 and tumor [J]. Journal of Modern Oncology, 2015, 23(7): 1002-1004.
[6] Yang X, Wu JS, Li M, et al. Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma [J]. J Exp Clin Cancer Res, 2021, 40(1): 169.
[7] 曹毛毛, 李贺, 孙殿钦, 等. 2000—2019年中国胃癌流行病学趋势分析[J]. 中华消化外科杂志, 2021, 20(1): 102-109. CAO Maomao, LI He, SUN Dianqin, et al. Epidemiological trend analysis of gastric cancer in China from 2000 to 2019 [J]. Chinese Journal Digestive Surgery, 2021, 20(1): 102-109.
[8] Lei ZN, Teng Q X, Tian Q, et al. Signaling pathways and therapeutic interventions in gastric cancer [J]. Signal Transduct Target Ther, 2022, 7(1): 358.
[9] Hirano A, Hsu PK, Zhang L, et al. DEC2 modulates orexin expression and regulates sleep [J]. Proc Natl Acad Sci U S A, 2018, 115(13): 3434-3439.
[10] Sato F, Kohsaka A, Bhawal UK, et al. Potential roles of Dec and Bmal1 genes in interconnecting circadian clock and energy metabolism [J]. Int J Mol Sci, 2018, 19(3):781.
[11] De Martin X, Sodaei R, Santpere G. Mechanisms of binding specificity among bHLH transcription factors [J]. Int J Mol Sci, 2021, 22(17): 9150. doi: 10.3390/ijms22179150.
[12] Zhang D, Zheng Q, Wang C, et al. BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway [J]. J Cell Mol Med, 2020, 24(7): 4001-4010.
[13] Nagata T, Minami K, Yamamoto M, et al. BHLHE41/DEC2 expression induces autophagic cell death in lung cancer cells and is associated with favorable prognosis for patients with lung adenocarcinoma [J]. Int J Mol Sci, 2021, 22(21): 11509. doi: 10.3390/ijms222111509.
[14] Bigot P, Colli LM, Machiela MJ, et al. Functional characterization of the 12p12.1 renal cancer-susceptibility locus implicates BHLHE41 [J]. Nat Commun, 2016, 7: 12098. doi: 10.1038/ncomms12098.
[15] Numata A, Kwok HS, Kawasaki A, et al. The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia [J]. Nat Commun, 2018, 9(1): 1622. doi: 10.1038/s41467-018-03854-0.
[16] Liu Q, Wu Y, Yoshizawa T, et al. Basic helix-loop-helix transcription factor DEC2 functions as an anti-apoptotic factor during paclitaxel-induced apoptosis in human prostate cancer cells [J]. Int J Molr Med, 2016, 38(6): 1727-1733.
[17] Li P, Jia YF, Ma XL, et al. DEC2 suppresses tumor proliferation and metastasis by regulating ERK/NF-κB pathway in gastric cancer [J]. Am J Cancer Res, 2016, 6(8): 1741-1757.
[18] Parks SK, Cormerais Y, Pouysségur J. Hypoxia and cellular metabolism in tumour pathophysiology [J]. J Physiol, 2017, 595(8): 2439-2450.
[19] Liao Y, Lu W, Che Q, et al. SHARP1 suppresses angiogenesis of endometrial cancer by decreasing hypoxia-inducible factor-1α level [J]. PLoS One, 2014, 9(6): e99907. doi: 10.1371/journal.pone.0099907.
[20] Chen S, Dong QJ, Wan ZA, et al. BHLHE41 overexpression alleviates the malignant behavior of colon cancer cells induced by hypoxia via modulating HIF-1α/EMT pathway [J]. Gastroenterol Res Pract, 2022, 2022: 6972331. doi: 10.1155/2022/6972331.
[21] Kusunose N, Akamine T, Kobayashi Y, et al. Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial(Müller)cells [J]. Jap J Ophthalmol, 2018, 62(6): 677-685.
[22] Befani C, Liakos P. The role of hypoxia-inducible factor-2 alpha in angiogenesis [J]. J Cell Physiol, 2018, 233(12): 9087-9098.
[23] Murugesan T, Rajajeyabalachandran G, Kumar S, et al. Targeting HIF-2α as therapy for advanced cancers [J]. Drug Discov Today, 2018, 23(7): 1444-1451.
[24] Wang Y, Li Z, Zhang H, et al. HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer [J]. Cancer Biol Ther, 2010, 10(4): 376-382.
[25] Tong WW, Tong GH, Chen XX, et al. HIF2α is associated with poor prognosis and affects the expression levels of survivin and cyclin D1 in gastric carcinoma [J]. Int J Oncol, 2015, 46(1): 233-242.
[26] Griffiths EA, Pritchard SA, Mcgrath SM, et al. Hypoxia-associated markers in gastric carcinogenesis and HIF-2α in gastric and gastro-oesophageal cancer prognosis [J]. Br J Cancer, 2008, 98(5): 965-973.
[27] Wu Y, Sato H, Suzuki T, et al. Involvement of c-Myc in the proliferation of MCF-7 human breast cancer cells induced by bHLH transcription factor DEC2 [J]. Int J Mol Med, 2015, 35(3): 815-820.
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