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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

miR-141-3p Enhanced Radiosensitivity of CRC Cells

Author(s): Lizhong Peng*, Pan Li and Zexu Peng

Volume 27, Issue 1, 2024

Published on: 23 June, 2023

Page: [118 - 126] Pages: 9

DOI: 10.2174/1386207326666230504144758

Price: $65

Abstract

Background: Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies, and numerous microRNAs (miRs) are identified to be active in CRC.

Objective: This work aimed to clarify the effect of miR-141-3p on the radiosensitivity of CRC cells.

Methods: Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6- MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after adding actinomycin-D. The role of DLX6- AS1 in the radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation- resistant CRC cells overexpressing miR-141-3p.

Results: The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR- 141-3p overexpression in amplifying the radiosensitivity of radiation-resistant CRC cells.

Conclusion: miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting the radiosensitivity of CRC cells.

Keywords: Colorectal cancer, miR-141-3p, lncRNA DLX6-AS1, radiotherapy, radiosensitivity, RNA stability, colon cancer, rectal cancer.

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[1]
Lichtenstern, C.R.; Ngu, R.K.; Shalapour, S.; Karin, M. Immunotherapy, inflammation and colorectal cancer. Cells, 2020, 9(3), 618.
[http://dx.doi.org/10.3390/cells9030618] [PMID: 32143413]
[2]
Dekker, E.; Tanis, P.J.; Vleugels, J.L.A.; Kasi, P.M.; Wallace, M.B. Colorectal cancer. Lancet, 2019, 394(10207), 1467-1480.
[http://dx.doi.org/10.1016/S0140-6736(19)32319-0] [PMID: 31631858]
[3]
Gong, L.; Zhang, Y.; Liu, C.; Zhang, M.; Han, S. Application of radiosensitizers in cancer radiotherapy. Int. J. Nanomedicine, 2021, 16, 1083-1102.
[http://dx.doi.org/10.2147/IJN.S290438] [PMID: 33603370]
[4]
Franzese, C.; Comito, T.; Toska, E.; Tozzi, A.; Clerici, E.; De Rose, F.; Franceschini, D.; Navarria, P.; Reggiori, G.; Tomatis, S.; Scorsetti, M. Predictive factors for survival of oligometastatic colorectal cancer treated with Stereotactic body radiation therapy. Radiother. Oncol., 2019, 133, 220-226.
[http://dx.doi.org/10.1016/j.radonc.2018.10.024] [PMID: 30414754]
[5]
Biller, L.H.; Schrag, D. Diagnosis and treatment of metastatic colorectal cancer. JAMA, 2021, 325(7), 669-685.
[http://dx.doi.org/10.1001/jama.2021.0106] [PMID: 33591350]
[6]
Liu, Y.P.; Zheng, C.C.; Huang, Y.N.; He, M.L.; Xu, W.W.; Li, B. Molecular mechanisms of chemo- and radiotherapy resistance and the potential implications for cancer treatment. MedComm, 2020, 2(3), 315-334.
[7]
Saliminejad, K.; Khorram Khorshid, H.R.; Soleymani Fard, S.; Ghaffari, S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol., 2019, 234(5), 5451-5465.
[http://dx.doi.org/10.1002/jcp.27486] [PMID: 30471116]
[8]
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]
[9]
Wang, H. MicroRNAs and Apoptosis in Colorectal Cancer. Int. J. Mol. Sci., 2020, 21(15), 5353.
[http://dx.doi.org/10.3390/ijms21155353] [PMID: 32731413]
[10]
Balacescu, O.; Sur, D.; Cainap, C.; Visan, S.; Cruceriu, D.; Manzat-Saplacan, R.; Muresan, M.S.; Balacescu, L.; Lisencu, C.; Irimie, A. The impact of miRNA in colorectal cancer progression and its liver metastases. Int. J. Mol. Sci., 2018, 19(12), 3711.
[http://dx.doi.org/10.3390/ijms19123711] [PMID: 30469518]
[11]
Noorolyai, S.; Mokhtarzadeh, A.; Baghbani, E.; Asadi, M.; Baghbanzadeh Kojabad, A.; Mogaddam, M.M.; Baradaran, B. The role of microRNAs involved in PI3‐kinase signaling pathway in colorectal cancer. J. Cell. Physiol., 2019, 234(5), 5664-5673.
[http://dx.doi.org/10.1002/jcp.27415] [PMID: 30488557]
[12]
Jafarzadeh, M.; Soltani, B.M. MiRNA‐Wnt signaling regulatory network in colorectal cancer. J. Biochem. Mol. Toxicol., 2021, 35(10), e22883.
[http://dx.doi.org/10.1002/jbt.22883] [PMID: 34382723]
[13]
Fanale, D.; Castiglia, M.; Bazan, V.; Russo, A. Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer. Adv. Exp. Med. Biol., 2016, 937, 207-228.
[http://dx.doi.org/10.1007/978-3-319-42059-2_11] [PMID: 27573902]
[14]
Xing, Y.; Jing, H.; Zhang, Y.; Suo, J.; Qian, M. MicroRNA-141-3p affected proliferation, chemosensitivity, migration and invasion of colorectal cancer cells by targeting EGFR. Int. J. Biochem. Cell Biol., 2020, 118, 105643.
[http://dx.doi.org/10.1016/j.biocel.2019.105643] [PMID: 31704502]
[15]
Moon, S.U.; Park, Y.; Park, M.G.; Song, S.K.; Jeong, S.H.; Lee, Y.S.; Heo, H.J.; Jung, W.Y.; Kim, S. Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway. Chem. Commun. (Camb.), 2019, 55(52), 7466-7469.
[http://dx.doi.org/10.1039/C9CC01944H] [PMID: 31184647]
[16]
Bridges, M.C.; Daulagala, A.C.; Kourtidis, A. LNCcation: lncRNA localization and function. J. Cell Biol., 2021, 220(2), e202009045.
[http://dx.doi.org/10.1083/jcb.202009045] [PMID: 33464299]
[17]
Ghafouri-Fard, S.; Hussen, B.M.; Gharebaghi, A.; Eghtedarian, R.; Taheri, M. LncRNA signature in colorectal cancer. Pathol. Res. Pract., 2021, 222, 153432.
[http://dx.doi.org/10.1016/j.prp.2021.153432] [PMID: 33857856]
[18]
Chen, S.; Shen, X. Long noncoding RNAs: Functions and mechanisms in colon cancer. Mol. Cancer, 2020, 19(1), 167.
[http://dx.doi.org/10.1186/s12943-020-01287-2] [PMID: 33246471]
[19]
Wang, L.; Cho, K.B.; Li, Y.; Tao, G.; Xie, Z.; Guo, B. Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int. J. Mol. Sci., 2019, 20(22), 5758.
[http://dx.doi.org/10.3390/ijms20225758] [PMID: 31744051]
[20]
Hu, C.; Liu, K.; Wang, B.; Xu, W.; Lin, Y.; Yuan, C. DLX6-AS1: An indispensable cancer-related long non-coding RNA. Curr. Pharm. Des., 2021, 27(9), 1211-1218.
[http://dx.doi.org/10.2174/1381612826666201029100151] [PMID: 33121401]
[21]
Zhang, J.J.; Xu, W.R.; Chen, B.; Wang, Y.Y.; Yang, N.; Wang, L.J.; Zhang, Y.L. The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3K/AKT/mTOR pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(19), 8321-8331.
[PMID: 31646562]
[22]
Zhang, R.; Tang, T.; Yu, H.M.; Yao, X.D. LncRNA DLX6-AS1/miR-129-5p/DLK1 axis aggravates stemness of osteosarcoma through Wnt signaling. Biochem. Biophys. Res. Commun., 2018, 507(1-4), 260-266.
[http://dx.doi.org/10.1016/j.bbrc.2018.11.019] [PMID: 30442366]
[23]
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]
[24]
Das, P.K.; Islam, F.; Lam, A.K. The roles of cancer stem cells and therapy resistance in colorectal carcinoma. Cells, 2020, 9(6), 1392.
[http://dx.doi.org/10.3390/cells9061392] [PMID: 32503256]
[25]
Liang, Z.; Li, X.; Liu, S.; Li, C.; Wang, X.; Xing, J. MiR-141–3p inhibits cell proliferation, migration and invasion by targeting TRAF5 in colorectal cancer. Biochem. Biophys. Res. Commun., 2019, 514(3), 699-705.
[http://dx.doi.org/10.1016/j.bbrc.2019.05.002] [PMID: 31078266]
[26]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(D1), D92-D97.
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[27]
Loher, P.; Rigoutsos, I. Interactive exploration of RNA22 microRNA target predictions. Bioinformatics, 2012, 28(24), 3322-3323.
[http://dx.doi.org/10.1093/bioinformatics/bts615] [PMID: 23074262]
[28]
Xing, T.; Chen, P.; Wu, J.; Gao, L.; Yang, W.; Cheng, Y.; Tong, L. UPF1 participates in the progression of endometrial cancer by inhibiting the expression of lncRNA PVT1. OncoTargets Ther., 2020, 13, 2103-2114.
[http://dx.doi.org/10.2147/OTT.S233149] [PMID: 32210576]
[29]
Mao, S.; Lu, Z.; Zheng, S.; Zhang, H.; Zhang, G.; Wang, F.; Huang, J.; Lei, Y.; Wang, X.; Liu, C.; Sun, N.; He, J. Exosomal miR-141 promotes tumor angiogenesis via KLF12 in small cell lung cancer. J. Exp. Clin. Cancer Res., 2020, 39(1), 193.
[http://dx.doi.org/10.1186/s13046-020-01680-1] [PMID: 32958011]
[30]
Ma, L.; Shao, H.; Chen, H.; Deng, Q. The mechanism of miR-141 regulating the proliferation and metastasis of liver cancer cells by targeting STAT4. J. Oncol., 2021, 2021, 1-9.
[http://dx.doi.org/10.1155/2021/5425491] [PMID: 34675977]
[31]
Fang, F.; Cheng, L.; Wu, X.; Ye, M.; Zhang, H. miR-141 promotes colon cancer cell proliferation by targeted PHLPP2 expression inhibitionn. Cancer Manag. Res., 2020, 12, 11341-11350.
[http://dx.doi.org/10.2147/CMAR.S256670] [PMID: 33204152]
[32]
Liu, S.; Wen, C. miR-141-3p promotes retinoblastoma progression via inhibiting sushi domain-containing protein 2. Bioengineered, 2022, 13(3), 7409-7423.
[http://dx.doi.org/10.1080/21655979.2022.2048770] [PMID: 35259051]
[33]
Chen, D.L.; Sheng, H.; Zhang, D.S.; Jin, Y.; Zhao, B.T.; Chen, N.; Song, K.; Xu, R.H. The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p. Mol. Cancer, 2021, 20(1), 166.
[http://dx.doi.org/10.1186/s12943-021-01475-8] [PMID: 34911533]
[34]
Tong, S.J.; Zhang, X.Y.; Guo, H.F.; Yang, J.; Qi, Y.P.; Lu, S. Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2. Clin. Transl. Oncol., 2021, 23(12), 2526-2535.
[http://dx.doi.org/10.1007/s12094-021-02653-2] [PMID: 34086253]
[35]
Wu, G.; Xue, M.; Zhao, Y.; Han, Y.; Li, C.; Zhang, S.; Zhang, J.; Xu, J. Long noncoding RNA ZEB1-AS1 acts as a Sponge of miR-141-3p to inhibit cell proliferation in colorectal cancer. Int. J. Med. Sci., 2020, 17(11), 1589-1597.
[http://dx.doi.org/10.7150/ijms.46698] [PMID: 32669962]
[36]
Findlay, V.J.; Wang, C.; Watson, D.K.; Camp, E.R. Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: Insights from cancer biology with therapeutic implications for colorectal cancer. Cancer Gene Ther., 2014, 21(5), 181-187.
[http://dx.doi.org/10.1038/cgt.2014.15] [PMID: 24787239]
[37]
Lin, S.; Chen, S.; Chen, Z.; Dai, Q.; Ke, C. X-ray-induced epithelial-mesenchymal transition in SW480 colorectal cancer cells and its potential mechanisms. J. BUON, 2017, 22(6), 1457-1462.
[PMID: 29332338]
[38]
Sun, Z.; Shao, B.; Liu, Z.; Dang, Q.; Guo, Y.; Chen, C.; Guo, Y.; Chen, Z.; Liu, J.; Hu, S.; Yuan, W.; Zhou, Q. LINC01296/miR-141-3p/ZEB1-ZEB2 axis promotes tumor metastasis via enhancing epithelial-mesenchymal transition process. J. Cancer, 2021, 12(9), 2723-2734.
[http://dx.doi.org/10.7150/jca.55626] [PMID: 33854632]
[39]
Qi, X.; Zhang, D.H.; Wu, N.; Xiao, J.H.; Wang, X.; Ma, W. ceRNA in cancer: Possible functions and clinical implications. J. Med. Genet., 2015, 52(10), 710-718.
[http://dx.doi.org/10.1136/jmedgenet-2015-103334] [PMID: 26358722]
[40]
Sun, Y.J.; Li, J.; Chen, C.H. Effects of miR-221 on the apoptosis of non-small cell lung cancer cells by lncRNA HOTAIR. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(10), 4226-4233.
[PMID: 31173294]
[41]
Ma, M.; Zhang, Y.; Weng, M.; Wang, S.; Hu, Y.; Hou, Z.; Qin, Y.; Gong, W.; Zhang, Y.J.; Kong, X.; Wang, J.; Quan, Z. Long noncoding RNA GCASPC, a target of miR-17-3p, negatively regulates pyruvate carboxylase–dependent cell proliferation in gallbladder cancer. Cancer Res., 2016, 76(18), 5361-5371.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3047] [PMID: 27450454]
[42]
Wu, D.M.; Zheng, Z.H.; Zhang, Y.B.; Fan, S.H.; Zhang, Z.F.; Wang, Y.J.; Zheng, Y.L.; Lu, J. Retraction Note: Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells. J. Exp. Clin. Cancer Res., 2022, 41(1), 121.
[http://dx.doi.org/10.1186/s13046-022-02347-9] [PMID: 35365213]
[43]
Guo, Q.; Sun, H.; Zheng, K.; Yin, S.; Niu, J. Long non-coding RNA DLX6-AS1/miR-141-3p axis regulates osteosarcoma proliferation, migration and invasion through regulating Rab10. RSC Advances, 2019, 9(58), 33823-33833.
[http://dx.doi.org/10.1039/C9RA05180E] [PMID: 35528911]
[44]
Kong, W.Q.; Liang, J.J.; Du, J.; Ye, Z.X.; Gao, P.; Liang, Y.L. Long noncoding RNA DLX6-AS1 regulates the growth and aggressiveness of colorectal cancer cells via mediating the miR-26a/EZH2 axis. Cancer Biother. Radiopharm., 2021, 36(9), 753-764.
[http://dx.doi.org/10.1089/cbr.2020.3589] [PMID: 32379493]
[45]
Mardanshahi, A.; Gharibkandi, N.A.; Vaseghi, S.; Abedi, S.M.; Molavipordanjani, S. The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines. Mol. Biol. Rep., 2021, 48(8), 1-14.
[http://dx.doi.org/10.1007/s11033-021-06607-3] [PMID: 34357550]

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