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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

TRIP13 Activates Glycolysis to Promote Cell Stemness and Strengthen Doxorubicin Resistance of Colorectal Cancer Cells

Author(s): Guangyi Liu, Huan Wang, Rui Ran, Yicheng Wang and Yang Li*

Volume 31, Issue 22, 2024

Published on: 12 February, 2024

Page: [3397 - 3411] Pages: 15

DOI: 10.2174/0109298673255498231117100421

Price: $65

Abstract

Background: Chemotherapy resistance is one of the main causes of clinical chemotherapy failure. Current cancer research explores the drug resistance mechanism and new therapeutic targets. This work aims to elucidate the mechanism of thyroid hormone receptor interactor 13 (TRIP13) affecting doxorubicin (DOX) resistance in colorectal cancer (CRC).

Methods: Bioinformatics analyses were employed to clarify TRIP13 expression in CRC tissues and predict the correlation of the TRIP13 enrichment pathway with glycolysis-related genes and stemness index mRNAsi. Quantitative real-time polymerase chain reaction and western blot were adopted to analyze the expression of TRIP13 and glycolysis- related genes. Cell Counting Kit-8 was utilized to determine the cell viability and IC50 value. Western blot was employed to measure the expression of stemness-related factors. Cell function assays were performed to detect cells' sphere-forming ability and glycolysis level. Animal models were constructed to determine the effects of TRIP13 expression on CRC tumor growth.

Results: TRIP13 was significantly overexpressed in CRC, concentrated in the glycolysis signaling pathway, and positively correlated with stemness index mRNAsi. High expression of TRIP13 facilitated DOX resistance in CRC. Further mechanistic studies revealed that overexpression of TRIP13 could promote cell stemness through glycolysis, which was also confirmed in animal experiments.

Conclusion: TRIP13 was highly expressed in CRC, which enhanced the DOX resistance of CRC cells by activating glycolysis to promote cell stemness. These findings offer new insights into the pathogenesis of DOX resistance in CRC and suggest that TRIP13 may be a new target for reversing DOX resistance in CRC.

« Previous Next »
[1]
Wen, J.; Min, X.; Shen, M.; Hua, Q.; Han, Y.; Zhao, L.; Liu, L.; Huang, G.; Liu, J.; Zhao, X. ACLY facilitates colon cancer cell metastasis by CTNNB1. . J. Exp. Clin. Cancer Res., 2019, 38(1), 401.
[2]
Xi, L.; Liu, Q.; Zhang, W.; Luo, L.; Song, J.; Liu, R.; Wei, S.; Wang, Y. Circular RNA circCSPP1 knockdown attenuates doxorubicin resistance and suppresses tumor progression of colorectal cancer via miR-944/FZD7 axis. Cancer Cell Int., 2021, 21(1), 153.
[http://dx.doi.org/10.1186/s12935-021-01855-6] [PMID: 33663510]
[3]
Lu, S.; Guo, M.; Fan, Z.; Chen, Y.; Shi, X.; Gu, C.; Yang, Y. Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer. Am. J. Transl. Res., 2019, 11(7), 4397-4410.
[PMID: 31396344]
[4]
Bian, X.; Chen, H.; Yang, P.; Li, Y.; Zhang, F.; Zhang, J.; Wang, W.; Zhao, W.; Zhang, S.; Chen, Q.; Zheng, Y.; Sun, X.; Wang, X.; Chien, K.Y.; Wu, Q. Nur77 suppresses hepatocellular carcinoma via switching glucose metabolism toward gluconeogenesis through attenuating phosphoenolpyruvate carboxykinase sumoylation. Nat. Commun., 2017, 8(1), 14420.
[http://dx.doi.org/10.1038/ncomms14420] [PMID: 28240261]
[5]
Li, W.; Xu, M.; Li, Y.; Huang, Z.; Zhou, J.; Zhao, Q.; Le, K.; Dong, F.; Wan, C.; Yi, P. Comprehensive analysis of the association between tumor glycolysis and immune/inflammation function in breast cancer. J. Transl. Med., 2020, 18(1), 92.
[http://dx.doi.org/10.1186/s12967-020-02267-2] [PMID: 32070368]
[6]
Li, C.; Zhang, G.; Zhao, L.; Ma, Z.; Chen, H. Metabolic reprogramming in cancer cells: glycolysis, glutaminolysis, and Bcl-2 proteins as novel therapeutic targets for cancer. World J. Surg. Oncol., 2015, 14(1), 15.
[http://dx.doi.org/10.1186/s12957-016-0769-9] [PMID: 26791262]
[7]
Chen, Z.; Hu, Z.; Sui, Q.; Huang, Y.; Zhao, M.; Li, M.; Liang, J.; Lu, T.; Zhan, C.; Lin, Z.; Sun, F.; Wang, Q.; Tan, L. LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/glycolysis axis in lung adenocarcinoma. Int. J. Biol. Sci., 2022, 18(2), 522-535.
[http://dx.doi.org/10.7150/ijbs.67556] [PMID: 35002507]
[8]
Fang, Z.; Sun, Q.; Yang, H.; Zheng, J. SDHB suppresses the tumorigenesis and development of ccRCC by inhibiting glycolysis. Front. Oncol., 2021, 11, 639408.
[http://dx.doi.org/10.3389/fonc.2021.639408] [PMID: 34094922]
[9]
Zhao, S.; Guan, B.; Mi, Y.; Shi, D.; Wei, P.; Gu, Y.; Cai, S.; Xu, Y.; Li, X.; Yan, D.; Huang, M.; Li, D. LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit. Oncogene, 2021, 40(28), 4709-4724.
[http://dx.doi.org/10.1038/s41388-021-01859-6] [PMID: 34145399]
[10]
Zhou, Y.; Tozzi, F.; Chen, J.; Fan, F.; Xia, L.; Wang, J.; Gao, G.; Zhang, A.; Xia, X.; Brasher, H.; Widger, W.; Ellis, L.M.; Weihua, Z. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res., 2012, 72(1), 304-314.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1674] [PMID: 22084398]
[11]
Shi, H.; Li, K.; Feng, J.; Zhang, X. Overexpression of long non-coding RNA urothelial carcinoma associated 1 causes paclitaxel (Taxol) resistance in colorectal cancer cells by promoting glycolysis. J. Chemother., 2021, 33(6), 409-419.
[http://dx.doi.org/10.1080/1120009X.2021.1906032] [PMID: 33818320]
[12]
Dai, S.; Peng, Y.; Zhu, Y.; Xu, D.; Zhu, F.; Xu, W.; Chen, Q.; Zhu, X.; Liu, T.; Hou, C.; Wu, J.; Miao, Y. Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine. Biomed. Pharmacother., 2020, 121, 109521.
[http://dx.doi.org/10.1016/j.biopha.2019.109521] [PMID: 31689601]
[13]
Agarwal, S.; Behring, M.; Kim, H.G.; Chandrashekar, D.S.; Chakravarthi, B.V.S.K.; Gupta, N.; Bajpai, P.; Elkholy, A.; Al Diffalha, S.; Datta, P.K.; Heslin, M.J.; Varambally, S.; Manne, U. TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status. Mol. Oncol., 2020, 14(12), 3007-3029.
[http://dx.doi.org/10.1002/1878-0261.12821] [PMID: 33037736]
[14]
Zhang, G.; Zhu, Q.; Fu, G.; Hou, J.; Hu, X.; Cao, J.; Peng, W.; Wang, X.; Chen, F.; Cui, H. TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis. Br. J. Cancer, 2019, 121(12), 1069-1078.
[http://dx.doi.org/10.1038/s41416-019-0633-0] [PMID: 31740732]
[15]
Zhou, X.Y.; Shu, X.M. TRIP13 promotes proliferation and invasion of epithelial ovarian cancer cells through Notch signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(2), 522-529.
[PMID: 30720159]
[16]
Zhang, L.T.; Ke, L.X.; Wu, X.Y.; Tian, H.T.; Deng, H.Z.; Xu, L.Y.; Li, E.M.; Long, L. TRIP13 induces nedaplatin resistance in esophageal squamous cell carcinoma by enhancing repair of DNA damage and inhibiting apoptosis. BioMed Res. Int., 2022, 2022, 1-16.
[http://dx.doi.org/10.1155/2022/7295458] [PMID: 35601150]
[17]
Ma, S.; Yang, D.; Liu, Y.; Wang, Y.; Lin, T.; Li, Y.; Yang, S.; Zhang, W.; Zhang, R. LncRNA BANCR promotes tumorigenesis and enhances adriamycin resistance in colorectal cancer. Aging, 2018, 10(8), 2062-2078.
[http://dx.doi.org/10.18632/aging.101530] [PMID: 30144787]
[18]
Zhang, Y.; Tang, B.; Song, J.; Yu, S.; Li, Y.; Su, H.; He, S. Lnc-PDZD7 contributes to stemness properties and chemosensitivity in hepatocellular carcinoma through EZH2-mediated ATOH8 transcriptional repression. J. Exp. Clin. Cancer Res., 2019, 38(1), 92.
[http://dx.doi.org/10.1186/s13046-019-1106-2] [PMID: 30786928]
[19]
Zhao, S.J.; Shen, Y.F.; Li, Q.; He, Y.J.; Zhang, Y.K.; Hu, L.P.; Jiang, Y.Q.; Xu, N.W.; Wang, Y.J.; Li, J.; Wang, Y.H.; Liu, F.; Zhang, R.; Yin, G.Y.; Tang, J.H.; Zhou, D.; Zhang, Z.G. SLIT2/ROBO1 axis contributes to the Warburg effect in osteosarcoma through activation of SRC/ERK/c-MYC/PFKFB2 pathway. Cell Death Dis., 2018, 9(3), 390.
[http://dx.doi.org/10.1038/s41419-018-0419-y] [PMID: 29523788]
[20]
Liu, X.; Shen, X.; Zhang, J. TRIP13 exerts a cancer-promoting role in cervical cancer by enhancing Wnt/β-catenin signaling via ACTN4. Environ. Toxicol., 2021, 36(9), 1829-1840.
[http://dx.doi.org/10.1002/tox.23303] [PMID: 34061428]
[21]
Cai, W.; Ni, W.; Jin, Y.; Li, Y. TRIP13 promotes lung cancer cell growth and metastasis through AKT/mTORC1/c-Myc signaling. Cancer Biomark., 2021, 30(2), 237-248.
[http://dx.doi.org/10.3233/CBM-200039] [PMID: 33136091]
[22]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[23]
Go, G.; Lee, C.S.; Yoon, Y.M.; Lim, J.H.; Kim, T.H.; Lee, S.H. PrPC aptamer conjugated–gold nanoparticles for targeted delivery of doxorubicin to colorectal cancer cells. Int. J. Mol. Sci., 2021, 22(4), 1976.
[http://dx.doi.org/10.3390/ijms22041976] [PMID: 33671292]
[24]
Huang, J.Q.; Li, H.F.; Zhu, J.; Song, J.W.; Zhang, X.B.; Gong, P.; Liu, Q.Y.; Zhou, C.H.; Wang, L.; Gong, L.Y. SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer. J. Transl. Med., 2021, 19(1), 280.
[http://dx.doi.org/10.1186/s12967-021-02954-8] [PMID: 34193174]
[25]
Agarwal, S.; Afaq, F.; Bajpai, P.; Kim, H.G.; Elkholy, A.; Behring, M.; Chandrashekar, D.S.; Diffalha, S.A.; Khushman, M.; Sugandha, S.P.; Varambally, S.; Manne, U. DCZ0415, a small-molecule inhibitor targeting TRIP13, inhibits EMT and metastasis via inactivation of the FGFR4/STAT3 axis and the Wnt/β-catenin pathway in colorectal cancer. Mol. Oncol., 2022, 16(8), 1728-1745.
[http://dx.doi.org/10.1002/1878-0261.13201] [PMID: 35194944]
[26]
Wang, Y.; Huang, J.; Li, B.; Xue, H.; Tricot, G.; Hu, L.; Xu, Z.; Sun, X.; Chang, S.; Gao, L.; Tao, Y.; Xu, H.; Xie, Y.; Xiao, W.; Yu, D.; Kong, Y.; Chen, G.; Sun, X.; Lian, F.; Zhang, N.; Wu, X.; Mao, Z.; Zhan, F.; Zhu, W.; Shi, J. A small-molecule inhibitor targeting TRIP13 suppresses multiple myeloma progression. Cancer Res., 2020, 80(3), 536-548.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-3987] [PMID: 31732653]
[27]
Lu, R.; Zhou, Q.; Ju, L.; Chen, L.; Wang, F.; Shao, J. Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway. Oncol. Rep., 2021, 46(2), 172.
[http://dx.doi.org/10.3892/or.2021.8123] [PMID: 34184074]
[28]
Chen, Y.; Chen, D.; Qin, Y.; Qiu, C.; Zhou, Y.; Dai, M.; Li, L.; Sun, Q.; Jiang, Y. TRIP13, identified as a hub gene of tumor progression, is the target of microRNA-4693-5p and a potential therapeutic target for colorectal cancer. Cell Death Discov., 2022, 8(1), 35.
[http://dx.doi.org/10.1038/s41420-022-00824-w] [PMID: 35075117]
[29]
Najafi, M.; Mortezaee, K.; Majidpoor, J. Cancer stem cell (CSC) resistance drivers. Life Sci., 2019, 234, 116781.
[http://dx.doi.org/10.1016/j.lfs.2019.116781] [PMID: 31430455]
[30]
Huang, R.; Rofstad, E.K. Cancer stem cells (CSCs), cervical CSCs and targeted therapies. Oncotarget, 2017, 8(21), 35351-35367.
[http://dx.doi.org/10.18632/oncotarget.10169] [PMID: 27343550]
[31]
Bayik, D.; Lathia, J.D. Cancer stem cell–immune cell crosstalk in tumour progression. Nat. Rev. Cancer, 2021, 21(8), 526-536.
[http://dx.doi.org/10.1038/s41568-021-00366-w] [PMID: 34103704]
[32]
Hao, Z.; Avci, U.; Tan, L.; Zhu, X.; Glushka, J.; Pattathil, S.; Eberhard, S.; Sholes, T.; Rothstein, G.E.; Lukowitz, W.; Orlando, R.; Hahn, M.G.; Mohnen, D. Loss of arabidopsis GAUT12/IRX8 causes anther indehiscence and leads to reduced G lignin associated with altered matrix polysaccharide deposition. Front. Plant Sci., 2014, 5, 357.
[http://dx.doi.org/10.3389/fpls.2014.00357] [PMID: 25120548]
[33]
Chi, J.; Zhang, H.; Hu, J.; Song, Y.; Li, J.; Wang, L.; Wang, Z. AGR3 promotes the stemness of colorectal cancer via modulating Wnt/β-catenin signalling. Cell. Signal., 2020, 65, 109419.
[http://dx.doi.org/10.1016/j.cellsig.2019.109419] [PMID: 31526829]
[34]
Qiu, L.; Yang, X.; Wu, J.; Huang, C.; Miao, Y.; Fu, Z. HIST2H2BF potentiates the propagation of cancer stem cells via notch signaling to promote malignancy and liver metastasis in colorectal carcinoma. Front. Oncol., 2021, 11, 677646.
[http://dx.doi.org/10.3389/fonc.2021.677646] [PMID: 34476209]
[35]
Li, H.; Chen, J.; Liu, J.; Lai, Y.; Huang, S.; Zheng, L.; Fan, N. CPT2 downregulation triggers stemness and oxaliplatin resistance in colorectal cancer via activating the ROS/Wnt/β-catenin-induced glycolytic metabolism. Exp. Cell Res., 2021, 409(1), 112892.
[http://dx.doi.org/10.1016/j.yexcr.2021.112892] [PMID: 34688609]
[36]
Shao, X.; Zheng, X.; Ma, D.; Liu, Y.; Liu, G. Inhibition of lncRNA-NEAT1 sensitizes 5-Fu resistant cervical cancer cells through de-repressing the microRNA-34a/LDHA axis. Biosci. Rep., 2021, 41(7), BSR20200533.
[http://dx.doi.org/10.1042/BSR20200533] [PMID: 33645623]
[37]
Wang, Y.; Lu, J.H.; Wu, Q.N.; Jin, Y.; Wang, D.S.; Chen, Y.X.; Liu, J.; Luo, X.J.; Meng, Q.; Pu, H.Y.; Wang, Y.N.; Hu, P.S.; Liu, Z.X.; Zeng, Z.L.; Zhao, Q.; Deng, R.; Zhu, X.F.; Ju, H.Q.; Xu, R.H. LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol. Cancer, 2019, 18(1), 174.
[http://dx.doi.org/10.1186/s12943-019-1105-0] [PMID: 31791342]
[38]
Dong, S.; Liang, S.; Cheng, Z.; Zhang, X.; Luo, L.; Li, L.; Zhang, W.; Li, S.; Xu, Q.; Zhong, M.; Zhu, J.; Zhang, G.; Hu, S. ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer. J. Exp. Clin. Cancer Res., 2022, 41(1), 15.
[http://dx.doi.org/10.1186/s13046-021-02229-6] [PMID: 34998404]
[39]
Yang, H.; Zhu, J.; Wang, G.; Liu, H.; Zhou, Y.; Qian, J. STK35 is ubiquitinated by NEDD4L and promotes glycolysis and inhibits apoptosis through regulating the AKT signaling pathway, influencing chemoresistance of colorectal cancer. Front. Cell Dev. Biol., 2020, 8, 582695.
[http://dx.doi.org/10.3389/fcell.2020.582695] [PMID: 33117809]

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