Wu J.a· Zhou F.b· Lai S.a· Wang W.a· Wu T.a· Liu Y.a· Yang L.c

Author affiliations

aDepartment of Anesthesiology, The Affiliated Hongdu Hospital of Traditional Chinese Medicine of Jiangxi University of Traditional Chinese Medicine, Nanchang, China
bDepartment of Urinary Surgery, Taian First People’s Hospital Affiliated to Shandong First Medical University, Taian, China
cDepartment of Anesthesiology, Hainan Hospital of PLA General Hospital, Sanya, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Received: March 16, 2022
Accepted: September 19, 2022
Published online: December 14, 2022

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

Introduction: Hepatocellular carcinoma (HCC) is the most deadly cancer. Many signal pathways are implicated in HCC development, including sonic hedgehog (SHH). Propofol is an anesthetic commonly used in surgery. Recent studies have reported that propofol inhibits tumorigenesis and the development of HCC in a dose-dependent manner. The study aimed to identify the mechanism of how the propofol-mediated SHH-signaling molecule works in HCC. Methods: Cell proliferation, apoptosis, and invasion were examined, respectively, through colony formation, TUNEL, caspase-3 activity, and transwell assays. Protein levels of SHH, Ptch1, Smo, and Gli1 were determined via Western blot. Results: Propofol could inhibit cell proliferation, migration, and invasion and induce apoptosis via suppression on SHH to inactivate the SHH pathway. By mechanistic assays, miR-340-5p was identified to target SHH and negatively regulate SHH. Long intergenic non-protein coding RNA 475 (LINC00475) was the endogenous sponge of miR-340-5p to upregulate SHH. Finally, the rescue assays were implemented. The activator of the SHH pathway completely rescued the effects of LINC00475 and SHH in propofol-induced HCC cells. Conclusion: Propofol inhibits HCC cell malignant behaviors via repressing LINC00475 to suppress SHH, thus inactivating the SHH pathway. These new findings might contribute to the understanding and application of propofol in HCC.

© 2022 S. Karger AG, Basel

References Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, et al. Erratum: whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet. 2016;48(6):700. Tamai T, Hayato S, Hojo S, Suzuki T, Okusaka T, Ikeda K, et al. Dose finding of lenvatinib in subjects with advanced hepatocellular carcinoma based on population pharmacokinetic and exposure-response analyses. J Clin Pharmacol. 2017;57(9):1138–47. Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, et al. Hepatocellular carcinoma: consensus recommendations of the national cancer institute clinical trials planning meeting. J Clin Oncol. 2010;28(25):3994–4005. Gluer AM, Cocco N, Laurence JM, Johnston ES, Hollands MJ, Pleass HC, et al. Systematic review of actual 10-year survival following resection for hepatocellular carcinoma. HPB. 2012;14(5):285–90. Liao X, Siu MK, Au CW, Wong ES, Chan HY, Ip PP, et al. Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis. 2009;30(1):131–40. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 2007;67(5):2187–96. Steinway SN, Zanudo JG, Ding W, Rountree CB, Feith DJ, Loughran TP Jr, et al. Network modeling of TGFβ signaling in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint sonic hedgehog and wnt pathway activation. Cancer Res. 2014;74(21):5963–77. Skoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the hedgehog signaling pathway in cancer: a comprehensive review. Bosn J Basic Med Sci. 2018;18(1):8–20. Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384(6605):129–34. Didiasova M, Schaefer L, Wygrecka M. Targeting GLI transcription factors in cancer. Molecules. 2018;23(5):1003. Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 2004;64(17):6071–4. Xu M, Li X, Liu T, Leng A, Zhang G. Prognostic value of hedgehog signaling pathway in patients with colon cancer. Med Oncol. 2012;29(2):1010–6. Fleck T, Schubert S, Ewert P, Stiller B, Nagdyman N, Berger F. Propofol effect on cerebral oxygenation in children with congenital heart disease. Pediatr Cardiol. 2015;36(3):543–9. Chen X, Wu Q, Sun P, Zhao Y, Zhu M, Miao C. Propofol disrupts aerobic glycolysis in colorectal cancer cells via inactivation of the NMDAR-CAMKII-ERK pathway. Cell Physiol Biochem. 2018;46(2):492–504. Wu ZF, Lee MS, Wong CS, Lu CH, Huang YS, Lin KT, et al. Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in colon cancer surgery. Anesthesiology. 2018;129(5):932–41. Zhang F, Wang C, Cui Y, Li S, Yao Y, Ci Y, et al. Effects of propofol on several membrane characteristics of cervical cancer cell lines. Cell Physiol Biochem. 2016;40(1–2):172–82. Meng C, Song L, Wang J, Li D, Liu Y, Cui X. Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231. Oncol Rep. 2017;37(2):841–8. Zhang L, Wang N, Zhou S, Ye W, Jing G, Zhang M. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2. J Exp Clin Cancer Res. 2012;31(1):66. Xiaoguang Z, Meirong L, Jingjing Z, Ruishen Z, Qing Z, Xiaofeng T. Long noncoding RNA CPS1-IT1 suppresses cell proliferation and metastasis in human lung cancer. Oncol Res. 2017;25(3):373–80. Yu X, Shi J, Wang X, Zhang F. Propofol affects the growth and metastasis of pancreatic cancer via ADAM8. Pharmacol Rep. 2020;72(2):418–26. Li Y, Dong W, Yang H, Xiao G. Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3. Biotechnol Lett. 2020;42(3):493–504. Ma X, Wang T, Zhao ZL, Jiang Y, Ye S. Propofol suppresses proinflammatory cytokine production by increasing ABCA1 expression via mediation by the long noncoding RNA LOC286367. Mediators Inflamm. 2018;2018:8907143. Wu X, Sui Z, Zhang H, Wang Y, Yu Z. Integrated analysis of lncRNA-mediated ceRNA network in lung adenocarcinoma. Front Oncol. 2020;10:554759. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92–7. Paraskevopoulou MD, Vlachos IS, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T, et al. DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res. 2016;44(D1):D231–8. Sanchez MA, Sullivan GM, Armstrong RC. Genetic detection of Sonic hedgehog (Shh) expression and cellular response in the progression of acute through chronic demyelination and remyelination. Neurobiol Dis. 2018;115:145–56. Chen YJ, Lin CP, Hsu ML, Shieh HR, Chao NK, Chao KS. Sonic hedgehog signaling protects human hepatocellular carcinoma cells against ionizing radiation in an autocrine manner. Int J Radiat Oncol Biol Phys. 2011;80(3):851–9. Hu YT, Li BF, Zhang PJ, Wu D, Li YY, Li ZW, et al. Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling. World J Gastroenterol. 2019;25(8):923–40. Zhang J, Shan WF, Jin TT, Wu GQ, Xiong XX, Jin HY, et al. Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells. J Transl Med. 2014;12(1):279. Chen Y, Zhao H, Li H, Feng X, Tang H, Qiu C, et al. LINC01234/MicroRNA-31-5p/MAGEA3 axis mediates the proliferation and chemoresistance of hepatocellular carcinoma cells. Mol Ther Nucleic Acids. 2020;19:168–78. Li X, Zhou Y, Yang L, Ma Y, Peng X, Yang S, et al. LncRNA NEAT1 promotes autophagy via regulating miR-204/ATG3 and enhanced cell resistance to sorafenib in hepatocellular carcinoma. J Cell Physiol. 2019;235(4):3402–13. Sui C, Dong Z, Yang C, Zhang M, Dai B, Geng L, et al. LncRNA FOXD2-AS1 as a competitive endogenous RNA against miR-150-5p reverses resistance to sorafenib in hepatocellular carcinoma. J Cell Mol Med. 2019;23(9):6024–33. Tang H, Wu Z, Zhang Y, Xia T, Liu D, Cai J, et al. Identification and function analysis of a five-long noncoding RNA prognostic signature for endometrial cancer patients. DNA Cell Biol. 2019;38(12):1480–98. Hou W, Tang Q, Bi F. Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2019;36(2):267–73. Mo X, Wu Y, Chen L, Zhai M, Gao Z, Hu K, et al. Global expression profiling of metabolic pathway-related lncRNAs in human gastric cancer and the identification of RP11-555H23.1 as a new diagnostic biomarker. J Clin Lab Anal. 2019;33(2):e22692. Li X, Yu M, Yang C. YY1-mediated overexpression of long noncoding RNA MCM3AP-AS1 accelerates angiogenesis and progression in lung cancer by targeting miR-340-5p/KPNA4 axis. J Cell Biochem. 2019;121(3):2258–67. Yang G, Yang C, She Y, Shen Z, Gao P. LINC01354 enhances the proliferation and invasion of lung cancer cells by regulating miR-340-5p/ATF1 signaling pathway. Artif Cells Nanomed Biotechnol. 2019;47(1):3737–44. Xiong Q, Wu S, Wang J, Zeng X, Chen J, Wei M, et al. Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p expression to induce STAT3 overexpression. Cell Biosci. 2017;7(1):16. Wu FQ, Fang T, Yu LX, Lv GS, Lv HW, Liang D, et al. ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. J Hepatol. 2016;65(2):314–24. Abd El Aziz MA, Facciorusso A, Nayfeh T, Saadi S, Elnaggar M, Cotsoglou C, et al. Immune checkpoint inhibitors for unresectable hepatocellular carcinoma. Vaccines. 2020;8(4):616. Facciorusso A, Abd El Aziz MA, Sacco R. Efficacy of regorafenib in hepatocellular carcinoma patients: a systematic review and meta-analysis. Cancers. 2019;12(1):36. Article / Publication Details

First-Page Preview

Received: March 16, 2022
Accepted: September 19, 2022
Published online: December 14, 2022

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.