Abstract
This study aimed to investigate the role of the long non-coding RNA (lncRNA) LINC00342-207 (LINC00342) in the development and progression of primary hepatocellular carcinoma (HCC). Forty-two surgically resected HCC tissues and corresponding paracancerous tissues were collected from October 2019 to December 2020 and examined for lncRNA LINC00342, microRNA (miR)-19a-3p, miR-545-5p, miR-203a-3p, cell cycle protein D1 (CyclinD1/CCND1), murine double minute 2 (MDM2), and fibroblast growth factor 2 (FGF2) expression. The disease-free survival and overall survival of patients with HCC were followed up. HCC cell lines and the normal hepatocyte cell line HL-7702 were cultured and the expression level of LINC00342 was measured. HepG2 cells were transfected with LINC00342 siRNA, LINC00342 overexpression plasmid, miR-19a-3p mimics and their corresponding suppressors, miR-545-5p mimics and their corresponding suppressors, and miR-203a-3p mimics and their corresponding suppressors. The proliferation, apoptosis, migration, and invasion of HepG2 cells were detected. Stably transfected HepG2 cells were inoculated into the left axilla of male BALB/c nude mice, and the volume and quality of transplanted tumors as well as the expression levels of LINC00342, miR-19a-3p, miR-545-5p, miR-203a-3p, CCND1, MDM2, and FGF2 were examined. LINC00342 played an oncogenic role in HCC and exhibited inhibitory effects on proliferation, migration, and invasion, and promoted the apoptosis of HepG2 cells. Moreover, it inhibited the growth of transplanted tumors in vivo in mice. Mechanistically, the oncogenic effect of LINC00342 was associated with the targeted regulation of the miR-19a-3p/CCND1, miR-545-5p/MDM2, and miR-203a-3p/FGF2 axes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
References
Asemota J, Saleh M, Igbinovia O, Burns D (2020) A concise review on current trends in imaging and surgical management of hepatocellular carcinoma. Cureus 12:e9191. https://doi.org/10.7759/cureus.9191
Azer SA (2018) MDM2-p53 interactions in human hepatocellular carcinoma: what is the role of nutlins and new therapeutic options? J Clin Med 7:64. https://doi.org/10.3390/jcm7040064
Bai Z, Li H, Li C, Sheng C, Zhao X (2020) Integrated analysis identifies a long non-coding RNAs-messenger RNAs signature for prediction of prognosis in hepatitis B virus-hepatocellular carcinoma patients. Medicine (baltimore) 99:e21503. https://doi.org/10.1097/md.0000000000021503
Chen QF, Kong JL, Zou SC, Gao H, Wang F, Qin SM, Wang W (2019) LncRNA LINC00342 regulated cell growth and metastasis in non-small cell lung cancer via targeting miR-203a-3p. Eur Rev Med Pharmacol Sci 23:7408–7418. https://doi.org/10.26355/eurrev_201909_18849
Chen Y, Zhou H, Wang Z, Huang Z, Wang J, Zheng M, Ni X, Liu L (2021) Integrated analysis of ceRNA network and tumor-infiltrating immune cells in esophageal cancer. Biosci Rep 41:BSR20203804. https://doi.org/10.1042/bsr20203804
Ding H, Wang Y, Zhang H (2020) CCND1 silencing suppresses liver cancer stem cell differentiation and overcomes 5-Fluorouracil resistance in hepatocellular carcinoma. J Pharmacol Sci 143:219–225. https://doi.org/10.1016/j.jphs.2020.04.006
Hartke J, Johnson M, Ghabril M (2017) The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol 34:153–159. https://doi.org/10.1053/j.semdp.2016.12.011
Hou H, Sun D, Zhang X (2019) The role of MDM2 amplification and overexpression in therapeutic resistance of malignant tumors. Cancer Cell Int 19:216. https://doi.org/10.1186/s12935-019-0937-4
Liu R, Yang X (2021) LncRNA LINC00342 promotes gastric cancer progression by targeting the miR-545-5p/CNPY2 axis. BMC Cancer 21:1163. https://doi.org/10.1186/s12885-021-08829-x
Liu S, Cao Q, An G, Yan B, Lei L (2020) Identification of the 3-lncRNA signature as a prognostic biomarker for colorectal cancer. Int J Mol Sci 21:9359. https://doi.org/10.3390/ijms21249359
Miao Z, Liu S, Xiao X, Li D (2020) LINC00342 regulates cell proliferation, apoptosis, migration and invasion in colon adenocarcinoma via miR-545-5p/MDM2 axis. Gene 743:144604. https://doi.org/10.1016/j.gene.2020.144604
Shen P, Qu L, Wang J, Ding Q, Zhou C, Xie R, Wang H, Ji G (2021) LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1 axis. Cancer Cell Int 21:105. https://doi.org/10.1186/s12935-020-01705-x
Sim HW, Knox J (2018) Hepatocellular carcinoma in the era of immunotherapy. Curr Probl Cancer 42:40–48. https://doi.org/10.1016/j.currproblcancer.2017.10.007
Stella SF, Noel-Lamy M, Rogalla P, Beecroft R, Rajan DK (2021) Hepatic arterial blood flow modulation in patients with hepatocellular carcinoma: a pilot study of the influence of intraarterial norepinephrine assessed with CT perfusion. J Vasc Interv Radiol 32:204–210. https://doi.org/10.1016/j.jvir.2020.08.006
Tang H, Zhao L, Li M, Li T, Hao Y (2019) Investigation of LINC00342 as a poor prognostic biomarker for human patients with non-small cell lung cancer. J Cell Biochem 120:5055–5061. https://doi.org/10.1002/jcb.27782
Wang L, Chen Z, An L, Wang Y, Zhang Z, Guo Y, Liu C (2016) Analysis of long non-coding RNA expression profiles in non-small cell lung cancer. Cell Physiol Biochem 38:2389–2400. https://doi.org/10.1159/000445591
Wang W, Cheng JW, Qin JJ, Hu B, Li X, Nijampatnam B, Velu SE, Fan J, Yang XR, Zhang R (2019) MDM2-NFAT1 dual inhibitor, MA242: effective against hepatocellular carcinoma, independent of p53. Cancer Lett 459:156–167. https://doi.org/10.1016/j.canlet.2019.114429
Wu SY, Lan SH, Liu HS (2019) Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis. Autophagy 15:729–730. https://doi.org/10.1080/15548627.2019.1569918
Xu M, Gu M, Zhang K, Zhou J, Wang Z, Da J (2015) miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2. Diagn Pathol 10:24. https://doi.org/10.1186/s13000-015-0255-7
Xu S, Wang Q, Kang Y, Liu J, Yin Y, Liu L, Wu H, Li S, Sui S, Shen M, Zheng W, Pang D (2020) Long noncoding RNAs control the modulation of immune checkpoint molecules in cancer. Cancer Immunol Res 8:937–951. https://doi.org/10.1158/2326-6066.cir-19-0696
Yang Y, Luo Z, Qin Y, Zhou Y, Gong L, Huang J, Wang H (2017) Production of bFGF monoclonal antibody and its inhibition of metastasis in Lewis lung carcinoma. Mol Med Rep 16:4015–4021. https://doi.org/10.3892/mmr.2017.7099
Yu Y, Ren K (2021) Five long non-coding RNAs establish a prognostic nomogram and construct a competing endogenous RNA network in the progression of non-small cell lung cancer. BMC Cancer 21:457. https://doi.org/10.1186/s12885-021-08207-7
Zhang Y, Guo X, Li Z, Li B, Li Z, Li R, Guo Q, Xiong L, Yu L, Zhao J, Lin N (2015) A systematic investigation based on microRNA-mediated gene regulatory network reveals that dysregulation of microRNA-19a/Cyclin D1 axis confers an oncogenic potential and a worse prognosis in human hepatocellular carcinoma. RNA Biol 12:643–657. https://doi.org/10.1080/15476286.2015.1022702
Zhang Y, Wang H, Zhou F, Hao A, Dai N, Yang H, Zheng A (2021) Identification of crucial long non-coding RNAs and mRNAs along with related regulatory networks through microarray analysis in esophageal carcinoma. Funct Integr Genomics 21:377–391. https://doi.org/10.1007/s10142-021-00784-x
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Author information
Authors and Affiliations
Contributions
Z-XY and J-HT designed the experiments and wrote the manuscript. Z-XY, J-HT, and Y-LL performed the experiments and analyzed the results. X-FX and LQ revised the manuscript. All the authors approved the final manuscript.
Corresponding authors
Ethics declarations
Competing Interests
The authors have no relevant financial or non-financial interests to disclose.
Ethical Approval
The study was approved by the ethics committee of The First Affiliated Hospital of Soochow University.
Consent to Participate
Informed consent was obtained from the enrolled patients.
Consent to Publish
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary file1 (ZIP 110294 KB)
Supplementary figure 1. Original images for WB.
Supplementary file2 (TIF 320 KB)
Supplementary figure 2. Copy number of lncRNA and miRNAs in HepG2 cells.
Supplementary file3 (PDF 626 KB)
Supplementary figure 3. Sanger sequence result of LINC00342.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yao, ZX., Tu, JH., Liu, YL. et al. Long Non-coding RNA LINC00342 Promotes the Proliferation, Invasion, and Migration of Primary Hepatocellular Carcinoma Cells by Regulating the Expression of miRNA-19a-3p, miRNA-545-5p, and miRNA-203a-3p. Biochem Genet 62, 675–697 (2024). https://doi.org/10.1007/s10528-023-10420-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-023-10420-x