Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Tectorigenin Inhibits Glycolysis-induced Cell Growth and Proliferation by Modulating LncRNA CCAT2/miR-145 Pathway in Colorectal Cancer

Author(s): Ying Xing, Bofan Lin, Baoxinzi Liu, Jie Shao and Zhichao Jin*

Volume 24, Issue 10, 2024

Published on: 11 January, 2024

Page: [1071 - 1079] Pages: 9

DOI: 10.2174/0115680096274757231219072003

open access plus

conference banner
Abstract

Background: Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin (Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies. However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported.

Objective: The objective of this study was to explore the action of Tec in proliferation and glycolysis in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA) CCAT2/micro RNA-145(miR-145) pathway in vitro and in vivo .

Methods: The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized to detect glucose consumption and lactate production in the supernatant of cells and animal serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime quantitative PCR (RT-qPCR).

Results: Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2 overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the expression of miR-145 increased after Tec treatment in vivo.

Conclusion: Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance for CRC treatment and new drug development.

Keywords: Tectorigenin, glycolysis, colorectal cancer, lncRNA CCAT2, microRNA-145, cell counting kit-8 (CCK-8).

« Previous Next »
Graphical Abstract

[1]
Hossain, M.S.; Karuniawati, H.; Jairoun, A.A.; Urbi, Z.; Ooi, D.J.; John, A.; Lim, Y.C.; Kibria, K.M.K.; Mohiuddin, A.K.M.; Ming, L.C.; Goh, K.W.; Hadi, M.A. Colorectal cancer: A review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers, 2022, 14(7), 1732.
[http://dx.doi.org/10.3390/cancers14071732] [PMID: 35406504]
[2]
Miller, K.D.; Nogueira, L.; Devasia, T.; Mariotto, A.B.; Yabroff, K.R.; Jemal, A.; Kramer, J.; Siegel, R.L. Cancer treatment and survivorship statistics, 2022. CA Cancer J. Clin., 2022, 72(5), 409-436.
[http://dx.doi.org/10.3322/caac.21731] [PMID: 35736631]
[3]
Holch, J.W.; Held, S.; Stintzing, S.; Fischer von Weikersthal, L.; Decker, T.; Kiani, A.; Kaiser, F.; Heintges, T.; Kahl, C.; Kullmann, F.; Scheithauer, W.; Moehler, M.; von Einem, J.C.; Michl, M.; Heinemann, V. Relation of cetuximab-induced skin toxicity and early tumor shrinkage in metastatic colorectal cancer patients: results of the randomized phase 3 trial FIRE-3 (AIO KRK0306). Ann. Oncol., 2020, 31(1), 72-78.
[http://dx.doi.org/10.1016/j.annonc.2019.10.001] [PMID: 31912799]
[4]
Ye, H.; Wang, K.; Lu, Q.; Zhao, J.; Wang, M.; Kan, Q.; Zhang, H.; Wang, Y.; He, Z.; Sun, J. Nanosponges of circulating tumor-derived exosomes for breast cancer metastasis inhibition. Biomaterials, 2020, 242, 119932.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119932] [PMID: 32169772]
[5]
Ye, H.; Wang, K.; Zhao, J.; Lu, Q.; Wang, M.; Sun, B.; Shen, Y.; Liu, H.; Pané, S.; Chen, X.Z.; He, Z.; Sun, J. In situ sprayed nanovaccine suppressing exosomal PD-L1 by golgi apparatus disorganization for postsurgical melanoma immunotherapy. ACS Nano, 2023, 17(11), 10637-10650.
[http://dx.doi.org/10.1021/acsnano.3c01733] [PMID: 37213184]
[6]
Ortíz, R.; Quiñonero, F.; García-Pinel, B.; Fuel, M.; Mesas, C.; Cabeza, L.; Melguizo, C.; Prados, J. Nanomedicine to overcome multidrug resistance mechanisms in colon and pancreatic cancer: Recent progress. Cancers (Basel), 2021, 13(9), 2058.
[http://dx.doi.org/10.3390/cancers13092058] [PMID: 33923200]
[7]
Karthika, C.; Sureshkumar, R.; Zehravi, M.; Akter, R.; Ali, F.; Ramproshad, S.; Mondal, B.; Kundu, M.K.; Dey, A.; Rahman, M.H.; Antonescu, A.; Cavalu, S. Multidrug resistance in cancer cells: Focus on a possible strategy plan to address colon carcinoma cells. Life, 2022, 12(6), 811.
[http://dx.doi.org/10.3390/life12060811] [PMID: 35743842]
[8]
Pavlova, N.N.; Zhu, J.; Thompson, C.B. The hallmarks of cancer metabolism: Still emerging. Cell Metab., 2022, 34(3), 355-377.
[http://dx.doi.org/10.1016/j.cmet.2022.01.007] [PMID: 35123658]
[9]
Zhong, X.; He, X.; Wang, Y.; Hu, Z.; Huang, H.; Zhao, S.; Wei, P.; Li, D. Warburg effect in colorectal cancer: The emerging roles in tumor microenvironment and therapeutic implications. J. Hematol. Oncol., 2022, 15(1), 160.
[http://dx.doi.org/10.1186/s13045-022-01358-5] [PMID: 36319992]
[10]
Chu, Z.; Huo, N.; Zhu, X.; Liu, H.; Cong, R.; Ma, L. FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect. Mol. Ther., 2021, 29(9), 2737-2753.
[http://dx.doi.org/10.1016/j.ymthe.2021.04.036]
[11]
Nava, G.M.; Madrigal Perez, L.A. Metabolic profile of the Warburg effect as a tool for molecular prognosis and diagnosis of cancer. Expert Rev. Mol. Diagn., 2022, 22(4), 439-447.
[http://dx.doi.org/10.1080/14737159.2022.2065196] [PMID: 35395916]
[12]
Jing, Z.; Liu, Q.; He, X.; Jia, Z.; Xu, Z.; Yang, B.; Liu, P. NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer. J. Exp. Clin. Cancer Res., 2022, 41(1), 198.
[http://dx.doi.org/10.1186/s13046-022-02412-3] [PMID: 35689245]
[13]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[14]
Takai, T.; Yoshikawa, Y.; Inamoto, T.; Minami, K.; Taniguchi, K.; Sugito, N.; Kuranaga, Y.; Shinohara, H.; Kumazaki, M.; Tsujino, T.; Takahara, K.; Ito, Y.; Akao, Y.; Azuma, H. A novel combination RNAi toward warburg effect by replacement with miR-145 and silencing of PTBP1 induces apoptotic cell death in bladder cancer cells. Int. J. Mol. Sci., 2017, 18(1), 179.
[http://dx.doi.org/10.3390/ijms18010179] [PMID: 28106737]
[15]
Zhang, S.; Pei, M.; Li, Z.; Li, H.; Liu, Y.; Li, J. Double‐negative feedback interaction between DNA methyltransferase 3A and microRNA‐145 in the Warburg effect of ovarian cancer cells. Cancer Sci., 2018, 109(9), 2734-2745.
[http://dx.doi.org/10.1111/cas.13734] [PMID: 29993160]
[16]
Yu, Y.; Nangia-Makker, P.; Farhana, L.; Majumdar, A.P.N. A novel mechanism of lncRNA and miRNA interaction: CCAT2 regulates miR-145 expression by suppressing its maturation process in colon cancer cells. Mol. Cancer, 2017, 16(1), 155.
[http://dx.doi.org/10.1186/s12943-017-0725-5] [PMID: 28964256]
[17]
Guo, T.; Li, Y.; Hong, S.; Cao, Q.; Chen, H.; Xu, Y.; Dai, G.; Shao, G. Evidence for anticancer effects of chinese medicine monomers on colorectal cancer. Chin. J. Integr. Med., 2022, 28(10), 939-952.
[http://dx.doi.org/10.1007/s11655-022-3466-2] [PMID: 35419728]
[18]
Guo, Y.; Chen, Y.H.; Cheng, Z.H.; Ou-Yang, H.N.; Luo, C.; Guo, Z.L. Tectorigenin inhibits osteosarcoma cell migration through downregulation of matrix metalloproteinases in vitro. Anticancer Drugs, 2016, 27(6), 540-546.
[http://dx.doi.org/10.1097/CAD.0000000000000362] [PMID: 26991068]
[19]
Amin, A.; Mokhdomi, T.A.; Bukhari, S.; Wani, S.H.; Wafai, A.H.; Lone, G.N. Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma. Pharmacol. Rep., 2015, 67(2), 382-387.
[http://dx.doi.org/10.1016/j.pharep.2014.10.020]
[20]
Jiang, C.P.; Ding, H.; Shi, D.H.; Wang, Y.R.; Li, E.G.; Wu, J.H. Pro-apoptotic effects of tectorigenin on human hepatocellular carcinoma HepG2 cells. World J. Gastroenterol., 2012, 18(15), 1753-1764.
[http://dx.doi.org/10.3748/wjg.v18.i15.1753] [PMID: 22553399]
[21]
Hu, T.; Liu, H.; Liang, Z.; Wang, F.; Zhou, C.; Zheng, X.; Zhang, Y.; Song, Y.; Hu, J.; He, X.; Xiao, J.; King, R.J.; Wu, X.; Lan, P. Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis. Theranostics, 2020, 10(9), 4056-4072.
[http://dx.doi.org/10.7150/thno.40860] [PMID: 32226539]
[22]
Hong, J.; Guo, F.; Lu, S.Y.; Shen, C.; Ma, D.; Zhang, X.; Xie, Y.; Yan, T.; Yu, T.; Sun, T.; Qian, Y.; Zhong, M.; Chen, J.; Peng, Y.; Wang, C.; Zhou, X.; Liu, J.; Liu, Q.; Ma, X.; Chen, Y.X.; Chen, H.; Fang, J.Y.F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer. Gut, 2021, 70(11), 2123-2137.
[http://dx.doi.org/10.1136/gutjnl-2020-322780] [PMID: 33318144]
[23]
Yu, S.; Zang, W.; Qiu, Y.; Liao, L.; Zheng, X. Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene, 2022, 41(1), 46-56.
[http://dx.doi.org/10.1038/s41388-021-02071-2] [PMID: 34671086]
[24]
Pirlog, R.; Drula, R.; Nutu, A.; Calin, G.A.; Berindan-Neagoe, I. The roles of the colon cancer associated transcript 2 (CCAT2) Long Non-Coding RNA in cancer: A comprehensive characterization of the tumorigenic and molecular functions. Int. J. Mol. Sci., 2021, 22(22), 12491.
[http://dx.doi.org/10.3390/ijms222212491] [PMID: 34830370]
[25]
Shen, S.N.; Li, K.; Liu, Y.; Yang, C.L.; He, C.Y.; Wang, H.R. RETRACTED: Silencing lncRNAs PVT1 upregulates mir-145 and confers inhibitory effects on viability, invasion, and migration in EC. Mol. Ther. Nucleic Acids, 2020, 19, 668-682.
[http://dx.doi.org/10.1016/j.omtn.2019.11.030] [PMID: 31951853]
[26]
Li, J.; Ma, X.; Chakravarti, D.; Shalapour, S.; DePinho, R.A. Genetic and biological hallmarks of colorectal cancer. Genes Dev., 2021, 35(11-12), 787-820.
[http://dx.doi.org/10.1101/gad.348226.120] [PMID: 34074695]
[27]
Vaupel, P.; Multhoff, G. Revisiting the warburg effect: historical dogma versus current understanding. J. Physiol., 2021, 599(6), 1745-1757.
[http://dx.doi.org/10.1113/JP278810] [PMID: 33347611]
[28]
Lunt, S.Y.; Vander Heiden, M.G. Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol., 2011, 27(1), 441-464.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154237] [PMID: 21985671]
[29]
Ghanavat, M.; Shahrouzian, M.; Deris Zayeri, Z.; Banihashemi, S.; Kazemi, S.M.; Saki, N. Digging deeper through glucose metabolism and its regulators in cancer and metastasis. Life Sci., 2021, 264, 118603.
[http://dx.doi.org/10.1016/j.lfs.2020.118603] [PMID: 33091446]
[30]
Li, M.; Chen, X.; Wang, X.; Wei, X.; Wang, D.; Liu, X.; Xu, L.; Batu, W.; Li, Y.; Guo, B.; Zhang, L. RSL3 enhances the antitumor effect of cisplatin on prostate cancer cells via causing glycolysis dysfunction. Biochem. Pharmacol., 2021, 192, 114741.
[http://dx.doi.org/10.1016/j.bcp.2021.114741] [PMID: 34428443]
[31]
Tan, P.; Li, M.; Liu, Z.; Li, T.; Zhao, L.; Fu, W. Glycolysis-Related LINC02432/Hsa-miR-98-5p/HK2 axis inhibits ferroptosis and predicts immune infiltration, tumor mutation burden, and drug sensitivity in pancreatic adenocarcinoma. Front. Pharmacol., 2022, 13, 937413.
[http://dx.doi.org/10.3389/fphar.2022.937413] [PMID: 35795552]
[32]
Yao, X.; Li, W.; Fang, D.; Xiao, C.; Wu, X.; Li, M. Emerging roles of energy metabolism in ferroptosis regulation of tumor cells. Adv. Sci., 2021, 8(22), 2100997.
[http://dx.doi.org/10.1002/advs.202100997]
[33]
Pan, Y.; Wang, W.; Huang, S.; Ni, W.; Wei, Z.; Cao, Y.; Yu, S.; Jia, Q.; Wu, Y.; Chai, C.; Zheng, Q.; Zhang, L.; Wang, A.; Sun, Z.; Huang, S.; Wang, S.; Chen, W.; Lu, Y. Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation. J. Cell. Mol. Med., 2019, 23(10), 6846-6858.
[http://dx.doi.org/10.1111/jcmm.14568] [PMID: 31343107]
[34]
Li, H.; Hu, S.; Pang, Y.; Li, M.; Chen, L.; Liu, F.; Liu, M.; Wang, Z.; Cheng, X. Bufalin inhibits glycolysis-induced cell growth and proliferation through the suppression of Integrin β2/FAK signaling pathway in ovarian cancer. Am. J. Cancer Res., 2018, 8(7), 1288-1296.
[PMID: 30094101]
[35]
Hou, J.; Chen, Q.; Huang, Y.; Wu, Z.; Ma, D. Caudatin blocks the proliferation, stemness and glycolysis of non-small cell lung cancer cells through the Raf/MEK/ERK pathway. Pharm. Biol., 2022, 60(1), 764-773.
[http://dx.doi.org/10.1080/13880209.2022.2050768] [PMID: 35387566]
[36]
Dai, Y.; Liu, Y.; Li, J.; Jin, M.; Yang, H.; Huang, G. Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway. Bioengineered, 2022, 13(5), 13906-13918.
[http://dx.doi.org/10.1080/21655979.2022.2086378] [PMID: 35706397]
[37]
Su, X.; Xue, C.; Xie, C.; Si, X.; Xu, J.; Huang, W.; Huang, Z.; Lin, J.; Chen, Z. lncRNA-LET regulates glycolysis and glutamine decomposition of esophageal squamous cell carcinoma through miR-93-5p/miR-106b-5p/SOCS4. Front. Oncol., 2022, 12, 897751.
[http://dx.doi.org/10.3389/fonc.2022.897751] [PMID: 35619921]
[38]
Zhai, S.; Xu, Z.; Xie, J.; Zhang, J.; Wang, X.; Peng, C.; Li, H.; Chen, H.; Shen, B.; Deng, X. Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1. Oncogene, 2021, 40(2), 277-291.
[http://dx.doi.org/10.1038/s41388-020-01525-3] [PMID: 33122827]
[39]
Xin, Y.; Li, Z.; Zheng, H.; Chan, M.T.V.; Ka Kei Wu, W. CCAT 2: A novel oncogenic long non‐coding RNA in human cancers. Cell Prolif., 2017, 50(3), e12342.
[http://dx.doi.org/10.1111/cpr.12342] [PMID: 28244168]
[40]
Chen, B.; Dragomir, M.P.; Fabris, L.; Bayraktar, R.; Knutsen, E.; Liu, X.; Tang, C.; Li, Y.; Shimura, T.; Ivkovic, T.C.; Cruz De los Santos, M.; Anfossi, S.; Shimizu, M.; Shah, M.Y.; Ling, H.; Shen, P.; Multani, A.S.; Pardini, B.; Burks, J.K.; Katayama, H.; Reineke, L.C.; Huo, L.; Syed, M.; Song, S.; Ferracin, M.; Oki, E.; Fromm, B.; Ivan, C.; Bhuvaneshwar, K.; Gusev, Y.; Mimori, K.; Menter, D.; Sen, S.; Matsuyama, T.; Uetake, H.; Vasilescu, C.; Kopetz, S.; Parker-Thornburg, J.; Taguchi, A.; Hanash, S.M.; Girnita, L.; Slaby, O.; Goel, A.; Varani, G.; Gagea, M.; Li, C.; Ajani, J.A.; Calin, G.A. The Long Noncoding RNA CCAT2 induces chromosomal instability through BOP1-AURKB Signaling. Gastroenterology, 2020, 159(6), 2146-2162.e33.
[http://dx.doi.org/10.1053/j.gastro.2020.08.018] [PMID: 32805281]
[41]
Wang, D.; Li, Z.; Yin, H. Long Non-Coding RNA CCAT2 activates rab14 and acts as an oncogene in colorectal cancer. Front. Oncol., 2021, 11, 751903.
[http://dx.doi.org/10.3389/fonc.2021.751903] [PMID: 34868956]
[42]
Redis, R.S.; Vela, L.E.; Lu, W.; Ferreira de Oliveira, J.; Ivan, C.; Rodriguez-Aguayo, C.; Adamoski, D.; Pasculli, B.; Taguchi, A.; Chen, Y.; Fernandez, A.F.; Valledor, L.; Van Roosbroeck, K.; Chang, S.; Shah, M.; Kinnebrew, G.; Han, L.; Atlasi, Y.; Cheung, L.H.; Huang, G.Y.; Monroig, P.; Ramirez, M.S.; Catela Ivkovic, T.; Van, L.; Ling, H.; Gafà, R.; Kapitanovic, S.; Lanza, G.; Bankson, J.A.; Huang, P.; Lai, S.Y.; Bast, R.C.; Rosenblum, M.G.; Radovich, M.; Ivan, M.; Bartholomeusz, G.; Liang, H.; Fraga, M.F.; Widger, W.R.; Hanash, S.; Berindan-Neagoe, I.; Lopez-Berestein, G.; Ambrosio, A.L.B.; Gomes Dias, S.M.; Calin, G.A. Allele-specific reprogramming of cancer metabolism by the long non-coding RNA CCAT2. Mol. Cell, 2016, 61(4), 520-534.
[http://dx.doi.org/10.1016/j.molcel.2016.01.015] [PMID: 26853146]
[43]
Zhang, Z.; Wang, X.; Wang, Y.; Zhou, D.; Wu, H.; Cheng, W.; Wang, Q.; Zheng, G.; Wang, J.; Gu, J. Effect of long noncoding RNA CCAT2 on drug sensitivity to 5‐fluorouracil of breast cancer cells through microRNA‐145 meditated by p53. J. Biochem. Mol. Toxicol., 2022, 36(11), e23176.
[http://dx.doi.org/10.1002/jbt.23176] [PMID: 35968984]
[44]
Moradi, F; Mohajerani, F; Sadeghizadeh, M CCAT2 knockdown inhibits cell growth, and migration and promotes apoptosis through regulating the hsa-mir-145-5p/AKT3/mTOR axis in tamoxifenresistant MCF7 cells. Life Sci, 2022, 311(Pt B), 121183.
[http://dx.doi.org/10.1016/j.lfs.2022.121183]
[45]
Niu, C.; Wang, L.; Ye, W.; Guo, S.; Bao, X.; Wang, Y.; Xia, Z.; Chen, R.; Liu, C.; Lin, X.; Huang, X. CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR‐145 maturation to induce MDM2 expression. J. Cell. Physiol., 2020, 235(9), 6307-6320.
[http://dx.doi.org/10.1002/jcp.29630] [PMID: 32037568]

Rights & Permissions Print Cite
Article Metrics
23
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy