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Effects of Pin1 on Proliferation and Apoptosis of HepG2 Cells Under Endoplasmic Reticulum Stress |
| JIANG Mingting1,2, HUANG Jing1,2, ZHENG Shuping3 |
| 1. Institute for Translational Medicine, Fujian Medical University, Fuzhou 350122, China; 2. Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases, Fuzhou 350122, China; 3. Public Technology Service Center, Fujian Medical University, Fuzhou 350122, China |
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Abstract Objective To investigate the expression of Pin1 protein in HepG2 cells under endoplasmic reticulum stress (ERS) and its effect on cell proliferation and apoptosis. Methods The THLE3 cells were treated with tunicamycin (TM) (TM group) or DMSO (DMSO group) for 48h. The HepG2 cells were treated with TM (TM group), ATRA(ATRA group), TM+ATRA (TM+ATRA group) or DMSO (DMSO group) for 48h. The protein levels of Bip and Pin1 were detected by Western blot, cell proliferation was detected by CCK-8 assay, and cell apoptosis was detected by flow cytometry. Results The expression of Bip both increased in THLE3 and HepG2 cells treated with TM, indicated that TM effectively induced ERS in cells. Compared with the DMSO group, the protein level of Pin1 in THLE3 cells in TM group was decreased with the increasing of TM concentration (P<0.001). In TM+ATRA group, with the increasing of TM concentration, the expression of Pin1 was decreased in HepG2 cells (P<0.01). The inhibitory rates was (29.33±4.73)% in HepG2 cells in TM group, significantly lower than (60.33±2.08)% in THLE3 cells in TM group (P<0.001). In TM+ATRA group, the growth inhibition rates was increased to (60.33±6.03)% in HepG2 cells. The apoptosis rate of THLE3 cells in TM group was (22.25±0.78)%, significantly higher than (3.57±0.31)% in DMSO group (P<0.01). The apoptosis rates of HepG2 cells in ATRA group and TM+ATRA group were significantly higher than that in the DMSO group ((10.03±0.49)% vs. (5.10±1.00)%, P<0.05 and (23.70±0.75)% vs. (5.10±1.00)%, P<0.01). Conclusion HepG2 cells resist ERS-induced apoptosis by maintaining Pin1 protein level. Reducing the protein level of Pin1 can significantly inhibit the cell proliferation and induce apoptosis.
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| Keywords
Pin1
Hepatocellular carcinoma
Cell proliferation
Apoptosis
Endoplasmic reticulum stress
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| Fund:Startup Fund for Scientific Research, Fujian Medical University (No. 2017XQ1004) |
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Issue Date: 16 June 2022
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[1] Almanza A, Carlesso A, Chintha C, et al. Endoplasmic
reticulum stress signalling- from basic mechanisms to clinical
applications[J]. FEBS J, 2019, 286(2): 241-278.
[2] Hu H, Tian M, Ding C, et al. The C/EBP Homologous Protein
(CHOP) Transcription Factor Functions in Endoplasmic
Reticulum Stress-Induced Apoptosis and Microbial Infection[J].
Front Immunol, 2019, 9: 3083.
[3] Chipurupalli S, Kannan E, Tergaonkar V, et al. Hypoxia Induced
ER Stress Response as an Adaptive Mechanism in Cancer[J]. Int J
Mol Sci, 2019, 20(3): 749.
[4] Oakes SA. Endoplasmic Reticulum Stress Signaling in Cancer
Cells[J]. Am J Pathol, 2020, 190(5): 934-946.
[5] Sisinni L, Pietrafesa M, Lepore S, et al. Endoplasmic Reticulum
Stress and Unfolded Protein Response in Breast Cancer: The
Balance between Apoptosis and Autophagy and Its Role in Drug
Resistance[J]. Int J Mol Sci, 2019, 20(4): 857.
[6] Siwecka N, Rozpedek W, Pytel D, et al. Dual role of Endoplasmic
Reticulum Stress-Mediated Unfolded Protein Response Signaling
Pathway in Carcinogenesis[J]. Int J Mol Sci, 2019, 20(18): 4354.
[7] Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular
carcinoma[J]. Nat Rev Dis Primers，2021, 7(1): 7.
[8] Villanueva A. Hepatocellular Carcinoma[J]. N Engl J Med, 2019,
380(15): 1450-1462.
[9] Fabregat I. Dysregulation of apoptosis in hepatocellular carcinoma
cells[J]. World J Gastroenterol, 2009, 15(5): 513-520.
[10] Wu XZ. New strategy of antiangiogenic therapy for hepatocellular
carcinoma[J]. Neoplasma, 2008, 55(6): 472-481.
[11 ] Yu JH, Im CY, Min SH. Function of PIN1 in Cancer Development
and Its Inhibitors as Cancer Therapeutics[J]. Front Cell Dev Biol,
2020, 8: 120.
[12] Pu W, Zheng Y, Peng Y. Prolyl Isomerase Pin1 in Human Cancer:
Function, Mechanism, and Significance[J]. Front Cell Dev Biol,
2020, 8: 168.
[13] Nakatsu Y, Matsunaga Y, Ueda K, et al. Development of Pin1 Inhibitors and their Potential as Therapeutic Agents[J]. Curr Med
Chem, 2020, 27(20): 3314-3329.
[14] Jeong K, Kim SJ, Oh Y, et al. p53 negatively regulates Pin1 expression under ER stress[J]. Biochem Biophys Res Commun,
2014, 454(4): 518-523.
[15] Bae JS, Noh SJ, Kim KM, et al. PIN1 in hepatocellular carcinoma
is associated with TP53 gene status[J]. Oncol Rep, 2016, 36(4):
2405-2411 .
[16] Lukas J, Pospech J, Oppermann C, et al. Role of endoplasmic
reticulum stress and protein misfolding in disorders of the liver
and pancreas[J]. Adv Med Sci, 2019, 64(2): 315-323.
[17] Zhang LJ, Chen S, Wu P, et al. Inhibition of MEK blocks GRP78
up-regulation and enhances apoptosis induced by ER stress in
gastric cancer cells[J]. Cancer Lett, 2009, 274(1): 40-46.
[18] Rampone B, Schiavone B, Martino A, et al. Current management
strategy of hepatocellular carcinoma[J]. World J Gastroenterol,
2009, 15(26): 3210-3216.
[19] Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug
Resistance in Cancer Chemotherapy[J]. Int J Mol Sci, 2020,
21(9): 3233. |
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