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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Cholangiocarcinoma | Research

ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells

Authors: Xueliang Li, Zhaowei Sun, Li Wang, Qinlei Wang, Maobing Wang, Jingyun Guo, Haoran Li, MenShou Chen, Guanghua Cao, Yanan Yu, Haochen Zhong, Hao Zou, Kai Ma, Bingyuan Zhang, Guolei Wang, Yujie Feng

Published in: BMC Cancer | Issue 1/2023

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Abstract

Long non-coding RNAs (lncRNAs) play important roles in many pathophysiological processes, including cancer progression. Namely, lncRNA Receptor-tyrosine-kinase-like orphan receptor-1 antisense 1 (ROR1-AS1) is crucial for cancer occurrence and progression in organs such as the liver or bladder. However, its expression and role in cholangiocarcinoma (CCA) have not been thoroughly explored.
Firstly, we assessed cell viability, proliferation, invasion, and migration using three cell lines (HuCCT-1, QBC399, and RBE) to explore the biological characteristics of ROR1-AS1 in CCA. Secondly, to determine the in vivo effect of ROR1-AS1 on tumor growth, ROR1-AS1 knockdown (KD) HuCCT-1 cells were subcutaneously injected into nude mice to evaluate tumor growth. Finally, we conducted a bioinformatic analysis to confirm the role of ROR1-AS1 in the prognosis and immunity of CCA.
In this study, we found that lncRNA ROR1-AS1 was increased in CCA samples and patients with higher ROR1-AS1 expression had a shorter overall survival period. siRNA-mediated KD of ROR1-AS1 significantly reduced cell proliferation and inhibited the migration of CCA cells. In addition, ROR1-AS1 KD HuCCT-1 cells injected into nude mice grew slower than normal CCA cells.
In summary, our results show that ROR1-AS1 can promote CCA progression and might serve as a new target for diagnosis and treatment of CCA.
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Literature
1.
go back to reference Bragazzi MC, Ridola L, Safarikia S, Matteo SD, Costantini D, Nevi L, Cardinale V. New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol. 2018;31(1):42–55.PubMed Bragazzi MC, Ridola L, Safarikia S, Matteo SD, Costantini D, Nevi L, Cardinale V. New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol. 2018;31(1):42–55.PubMed
3.
go back to reference Golan T, Raitses-Gurevich M, Kelley RK, Bocobo AG, Borgida A, Shroff RT, Holter S, Gallinger S, Ahn DH, Aderka D, et al. Overall survival and clinical characteristics of BRCA-Associated Cholangiocarcinoma: a Multicenter Retrospective Study. Oncologist. 2017;22(7):804–10.CrossRefPubMedPubMedCentral Golan T, Raitses-Gurevich M, Kelley RK, Bocobo AG, Borgida A, Shroff RT, Holter S, Gallinger S, Ahn DH, Aderka D, et al. Overall survival and clinical characteristics of BRCA-Associated Cholangiocarcinoma: a Multicenter Retrospective Study. Oncologist. 2017;22(7):804–10.CrossRefPubMedPubMedCentral
4.
go back to reference Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145(6):1215–29.CrossRefPubMed Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145(6):1215–29.CrossRefPubMed
5.
go back to reference Balakrishnan A, Goodpaster T, Randolph-Habecker J, Hoffstrom BG, Jalikis FG, Koch LK, Berger C, Kosasih PL, Rajan A, Sommermeyer D, et al. Analysis of ROR1 protein expression in Human Cancer and normal tissues. Clin Cancer Res. 2017;23(12):3061–71.CrossRefPubMed Balakrishnan A, Goodpaster T, Randolph-Habecker J, Hoffstrom BG, Jalikis FG, Koch LK, Berger C, Kosasih PL, Rajan A, Sommermeyer D, et al. Analysis of ROR1 protein expression in Human Cancer and normal tissues. Clin Cancer Res. 2017;23(12):3061–71.CrossRefPubMed
6.
go back to reference Masiakowski P, Carroll RD. A novel family of cell surface receptors with tyrosine kinase-like domain. J Biol Chem. 1992;267(36):26181–90.CrossRefPubMed Masiakowski P, Carroll RD. A novel family of cell surface receptors with tyrosine kinase-like domain. J Biol Chem. 1992;267(36):26181–90.CrossRefPubMed
7.
go back to reference Hu G, Gupta SK, Troska TP, Nair A, Gupta M. Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex. Oncotarget. 2017;8(46):80223–34.CrossRefPubMedPubMedCentral Hu G, Gupta SK, Troska TP, Nair A, Gupta M. Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex. Oncotarget. 2017;8(46):80223–34.CrossRefPubMedPubMedCentral
8.
go back to reference Zhang L, Yao HR, Liu SK, Song LL. Long noncoding RNA ROR1–AS1 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in cervical cancer. Eur Rev Med Pharmacol Sci. 2020;24(6):2928–37.PubMed Zhang L, Yao HR, Liu SK, Song LL. Long noncoding RNA ROR1–AS1 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in cervical cancer. Eur Rev Med Pharmacol Sci. 2020;24(6):2928–37.PubMed
9.
go back to reference Wang FZ, Zhang MQ, Zhang L, Zhang MC. Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375. Eur Rev Med Pharmacol Sci. 2021;25(4):1764.PubMed Wang FZ, Zhang MQ, Zhang L, Zhang MC. Long non-coding RNA ROR1-AS1 enhances colorectal cancer metastasis by targeting miR-375. Eur Rev Med Pharmacol Sci. 2021;25(4):1764.PubMed
10.
go back to reference Xu N, Qiao L, Yin L, Li H. Long noncoding RNA ROR1-AS1 enhances lung adenocarcinoma metastasis and induces epithelial-mesenchymal transition by sponging miR-375. J buon. 2019;24(6):2273–9.PubMed Xu N, Qiao L, Yin L, Li H. Long noncoding RNA ROR1-AS1 enhances lung adenocarcinoma metastasis and induces epithelial-mesenchymal transition by sponging miR-375. J buon. 2019;24(6):2273–9.PubMed
11.
go back to reference Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(W1):W509–w514.CrossRefPubMedPubMedCentral Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(W1):W509–w514.CrossRefPubMedPubMedCentral
12.
go back to reference Zhang Z, Wang S, Yang F, Meng Z, Liu Y. LncRNA ROR1–AS1 high expression and its prognostic significance in liver cancer. Oncol Rep. 2020;43(1):55–74.PubMed Zhang Z, Wang S, Yang F, Meng Z, Liu Y. LncRNA ROR1–AS1 high expression and its prognostic significance in liver cancer. Oncol Rep. 2020;43(1):55–74.PubMed
13.
go back to reference Liao T, Maierdan SL, Lv C. ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/β-catenin. Eur Rev Med Pharmacol Sci. 2020;24(14):7561.PubMed Liao T, Maierdan SL, Lv C. ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/β-catenin. Eur Rev Med Pharmacol Sci. 2020;24(14):7561.PubMed
14.
go back to reference Zhang Z, Zhou Y, Hu K, Wang D, Wang Z, Huang Y. Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study. BMC Cancer. 2020;20(1):270.CrossRefPubMedPubMedCentral Zhang Z, Zhou Y, Hu K, Wang D, Wang Z, Huang Y. Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study. BMC Cancer. 2020;20(1):270.CrossRefPubMedPubMedCentral
15.
go back to reference Meng XL, Lu JC, Zeng HY, Chen Z, Guo XJ, Gao C, Pei YZ, Hu SY, Ye M, Sun QM, et al. The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion. Hepatol Int. 2023;17(1):63–76.CrossRefPubMed Meng XL, Lu JC, Zeng HY, Chen Z, Guo XJ, Gao C, Pei YZ, Hu SY, Ye M, Sun QM, et al. The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion. Hepatol Int. 2023;17(1):63–76.CrossRefPubMed
16.
go back to reference Wang SY, Jiang N, Zeng JP, Yu SQ, Xiao Y, Jin S. Characteristic of Perineural Invasion in Hilar Cholangiocarcinoma based on whole-mount histologic large sections of liver. Front Oncol. 2022;12:855615.CrossRefPubMedPubMedCentral Wang SY, Jiang N, Zeng JP, Yu SQ, Xiao Y, Jin S. Characteristic of Perineural Invasion in Hilar Cholangiocarcinoma based on whole-mount histologic large sections of liver. Front Oncol. 2022;12:855615.CrossRefPubMedPubMedCentral
17.
go back to reference Li F, Gu F, Li Q, Zhai C, Gong R, Zhu X. ROR1-AS1 knockdown inhibits growth and invasion and promotes apoptosis in NSCLC cells by suppression of the PI3K/Akt/mTOR pathway. J Biochem Mol Toxicol. 2021;35(5):e22726.CrossRefPubMed Li F, Gu F, Li Q, Zhai C, Gong R, Zhu X. ROR1-AS1 knockdown inhibits growth and invasion and promotes apoptosis in NSCLC cells by suppression of the PI3K/Akt/mTOR pathway. J Biochem Mol Toxicol. 2021;35(5):e22726.CrossRefPubMed
18.
go back to reference Chen Q, Fu L. Upregulation of long non-coding RNA ROR1-AS1 promotes cell growth and migration in bladder cancer by regulation of miR-504. PLoS ONE. 2020;15(1):e0227568.CrossRefPubMedPubMedCentral Chen Q, Fu L. Upregulation of long non-coding RNA ROR1-AS1 promotes cell growth and migration in bladder cancer by regulation of miR-504. PLoS ONE. 2020;15(1):e0227568.CrossRefPubMedPubMedCentral
19.
go back to reference Wang S, Chen W, Yu H, Song Z, Li Q, Shen X, Wu Y, Zhu L, Ma Q, Xing D. lncRNA ROR promotes gastric Cancer Drug Resistance. Cancer Control. 2020;27(1):1073274820904694.CrossRefPubMedPubMedCentral Wang S, Chen W, Yu H, Song Z, Li Q, Shen X, Wu Y, Zhu L, Ma Q, Xing D. lncRNA ROR promotes gastric Cancer Drug Resistance. Cancer Control. 2020;27(1):1073274820904694.CrossRefPubMedPubMedCentral
20.
go back to reference Li X, Zuo C, Wu M, Zhang Z. Linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity. Metallomics. 2020;12(6):963–73.CrossRefPubMed Li X, Zuo C, Wu M, Zhang Z. Linc-ROR promotes arsenite-transformed keratinocyte proliferation by inhibiting P53 activity. Metallomics. 2020;12(6):963–73.CrossRefPubMed
21.
go back to reference Wallstabe L, Göttlich C, Nelke LC, Kühnemundt J, Schwarz T, Nerreter T, Einsele H, Walles H, Dandekar G, Nietzer SL et al. ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models. JCI Insight 2019, 4(18). Wallstabe L, Göttlich C, Nelke LC, Kühnemundt J, Schwarz T, Nerreter T, Einsele H, Walles H, Dandekar G, Nietzer SL et al. ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models. JCI Insight 2019, 4(18).
22.
go back to reference Aponte-López A, Muñoz-Cruz S. Mast cells in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1273:159–73.CrossRefPubMed Aponte-López A, Muñoz-Cruz S. Mast cells in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1273:159–73.CrossRefPubMed
23.
24.
go back to reference Kamrani A, Mehdizadeh A, Ahmadi M, Aghebati-Maleki L, Yousefi M. Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells. Expert Opin Ther Targets. 2019;23(5):447–56.CrossRefPubMed Kamrani A, Mehdizadeh A, Ahmadi M, Aghebati-Maleki L, Yousefi M. Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells. Expert Opin Ther Targets. 2019;23(5):447–56.CrossRefPubMed
25.
go back to reference Hojjat-Farsangi M, Moshfegh A, Daneshmanesh AH, Khan AS, Mikaelsson E, Osterborg A, Mellstedt H. The receptor tyrosine kinase ROR1–an oncofetal antigen for targeted cancer therapy. Semin Cancer Biol. 2014;29:21–31.CrossRefPubMed Hojjat-Farsangi M, Moshfegh A, Daneshmanesh AH, Khan AS, Mikaelsson E, Osterborg A, Mellstedt H. The receptor tyrosine kinase ROR1–an oncofetal antigen for targeted cancer therapy. Semin Cancer Biol. 2014;29:21–31.CrossRefPubMed
26.
go back to reference Shabani M, Naseri J, Shokri F. Receptor tyrosine kinase-like orphan receptor 1: a novel target for cancer immunotherapy. Expert Opin Ther Targets. 2015;19(7):941–55.CrossRefPubMed Shabani M, Naseri J, Shokri F. Receptor tyrosine kinase-like orphan receptor 1: a novel target for cancer immunotherapy. Expert Opin Ther Targets. 2015;19(7):941–55.CrossRefPubMed
Metadata
Title
ROR1-AS1 might promote in vivo and in vitro proliferation and invasion of cholangiocarcinoma cells
Authors
Xueliang Li
Zhaowei Sun
Li Wang
Qinlei Wang
Maobing Wang
Jingyun Guo
Haoran Li
MenShou Chen
Guanghua Cao
Yanan Yu
Haochen Zhong
Hao Zou
Kai Ma
Bingyuan Zhang
Guolei Wang
Yujie Feng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11412-1

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