Abstract
LINC00467 was reported as an oncogenic gene in different types of human cancers. In this study, we investigated the molecular mechanisms of LINC00467 in the tumorigenesis of laryngeal squamous cell cancer (LSCC). RT-qPCR was utilized to detect the mRNA expression of genes, and western blot assay was used to determine the protein levels of TNF alpha-induced protein 3 (TNFAIP3). The cell viability was detected by CCK-8 assay. Transwell assays were conducted to determine the cell migration and invasion of LSCC cells, and the cell cycle was assessed by flow cytometry. The association between paired box 5 (PAX5), LINC00467, miR-4735-3p, and TNFAIP3 was verified using ChIP, RNA pull-down, or luciferase reporter assays. In our study, we found that LINC00467 was upregulated in LSCC, and knockdown of LINC00467 suppressed cell viability and metastasis of LSCC. Besides, LINC00467 transcription could be activated by PAX5 in LSCC. Furthermore, LINC00467 acted as competitive endogenous RNA (ceRNA) for miR-4735-3p to accelerate LSCC progression. In the meantime, TNFAIP3 was identified as a downstream gene of miR-4735-3p. Finally, TNFAIP3 overexpression could overturn the effects of miR-4735-3p mimic on LSCC cellular activities. In conclusion, our results demonstrated that PAX5-induced LINC00467 facilitated LSCC progression by inhibiting miR-4735-3p to increase TNFAIP3 expression.
Similar content being viewed by others
Change history
31 October 2022
A Correction to this paper has been published: https://doi.org/10.1007/s12033-022-00583-0
References
Li, Y., Tao, C., Dai, L., Cui, C., Chen, C., Wu, H., Wei, Q., & Zhou, X. (2019). MicroRNA-625 inhibits cell invasion and epithelial-mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma. Bioscience Reports. https://doi.org/10.1042/BSR20181882
Wang, X., Yu, B., Jin, Q., Zhang, J., Yan, B., Yang, L., Li, Y., Li, Q., Wang, P., Sun, C., & Liu, M. (2020). Regulation of laryngeal squamous cell cancer progression by the lncRNA RP11–159K7.2/miR-206/DNMT3A axis. Journal of Cellular and Molecular Medicine, 24(12), 6781–6795.
Liu, Y., Liu, X., Zhang, X., Deng, J., Zhang, J., & Xing, H. (2020). lncRNA DLX6-AS1 promotes proliferation of laryngeal cancer cells by targeting the miR-26a/TRPC3 pathway. Cancer Management and Research, 12, 2685–2695.
Tian, C., Yang, Y., Ke, Y., Yang, L., Zhong, L., Wang, Z., & Huang, H. (2021). Integrative analyses of genes associated with right ventricular cardiomyopathy induced by tricuspid regurgitation. Frontiers in Genetics, 12, 708275.
Feng, R. M., Zong, Y. N., Cao, S. M., & Xu, R. H. (2019). Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond), 39(1), 22.
Pan, J., Lu, L., Wang, X., Liu, D., Tian, J., Liu, H., Zhang, M., Xu, F., & An, F. (2018). AIM2 regulates vascular smooth muscle cell migration in atherosclerosis. Biochemical and Biophysical Research Communications, 497(1), 401–409.
Nie, K., Deng, Z., Zheng, Z., Wen, Y., Pan, J., Jiang, X., Yan, Y., Liu, P., Liu, F., & Li, P. (2020). Identification of a 14-lncRNA signature and construction of a prognostic nomogram predicting overall survival of gastric cancer. DNA and Cell Biology, 39(9), 1532–1544.
Cao, J., Yang, Z., An, R., Zhang, J., Zhao, R., Li, W., Xu, L., Sun, Y., & Liu, M. (2020). lncRNA IGKJ2-MALLP2 suppresses LSCC proliferation, migration, invasion, and angiogenesis by sponging miR-1911–3p/p21. Cancer Science, 111(9), 3245–3257.
Wei, C., Wei, H., Wu, X., Nong, G., Wu, C., Lee, J., Meng, N., Yu, D., Su, J., Guo, M., & Qin, J. (2020). LncRNA-IUR sponges miR-24 to upregulate P53 in laryngeal squamous cell carcinoma. Cancer Management and Research, 12, 11639–11647.
Huang, M. J., Zhao, J. Y., Xu, J. J., Li, J., Zhuang, Y. F., & Zhang, X. L. (2019). lncRNA ADAMTS9-AS2 controls human mesenchymal stem cell chondrogenic differentiation and functions as a ceRNA. Molecular Therapy Nucleic acids, 18, 533–545.
Li, W., Chen, Y., & Nie, X. (2020). Regulatory mechanisms of lncRNAs and their target gene signaling pathways in laryngeal squamous cell carcinoma. Frontiers in Pharmacology, 11, 1140.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4), 402–408.
Dong, H., Wang, W., Mo, S., Chen, R., Zou, K., Han, J., Zhang, F., & Hu, J. (2018). SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88. Journal of Experimental & Clinical Cancer Research: CR, 37(1), 202.
You, Q., Yao, Y., Wu, J., Cheng, C., Li, Y., & Yuan, H. (2020). YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis. Biomedicine & Pharmacotherapy, 129, 110339.
Wang, H., Huo, X., Yang, X. R., He, J., Cheng, L., Wang, N., Deng, X., Jin, H., Wang, N., Wang, C., & Zhao, F. (2017). STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Molecular Cancer, 16(1), 136.
Lyu, K., Li, Y., Xu, Y., & Yue, H. (2020). Using RNA sequencing to identify a putative lncRNA-associated ceRNA network in laryngeal squamous cell carcinoma. RNA Biology, 17(7), 977–989.
Jiang, Q., Liu, S., Hou, L., Guan, Y., & Yang, S. (2020). The implication of LncRNA MALAT1 in promoting chemo-resistance of laryngeal squamous cell carcinoma cells. Journal of Clinical Laboratory Analysis, 34(4), e23116.
Li, S., Teng, Y., Yuan, M. J., Ma, T. T., Ma, J., & Gao, X. J. (2020). A seven long-noncoding RNA signature predicts prognosis of lung squamous cell carcinoma. Biomarkers in Medicine, 14(1), 53–63.
Zhu, Y., Li, J., Bo, H., He, D., Xiao, M., Xiang, L., Gong, L., Hu, Y., Zhang, Y., Cheng, Y., & Deng, L. (2020). LINC00467 is up-regulated by TDG-mediated acetylation in non-small cell lung cancer and promotes tumor progression. Oncogene, 39(38), 6071–6084.
Jiang, W., Cheng, X., Wang, T., Song, X., Zheng, Y., & Wang, L. (2020). LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma. The Journal of Gene Medicine, 22(3), e3134.
Ma, H. Z., Wang, J., Shi, J., Zhang, W., & Zhou, D. S. (2020). LncRNA LINC00467 contributes to osteosarcoma growth and metastasis through regulating HMGA1 by directly targeting miR-217. European Review for Medical and Pharmacological Sciences, 24(11), 5933–5945.
Kong, X., Duan, Y., Sang, Y., & Li, Y. (2019). LncRNA-CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA-215. Journal of Cellular Physiology, 234(6), 9105–9117.
Yang, X. Z., Cheng, T. T., He, Q. J., Lei, Z. Y., Chi, J., Tang, Z., Liao, Q. X., Zhang, H., Zeng, L. S., & Cui, S. Z. (2018). LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Molecular Cancer, 17(1), 126.
Luan, X., & Wang, Y. (2018). LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331–3p and miR-338–3p. Journal of Gynecologic Oncology, 29(6), e95.
Teng, J., Ai, X., Jia, Z., Wang, K., Guan, Y., & Guo, Y. (2019). Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis. Cancer Biology & Therapy, 20(4), 552–561.
Luo, M., Kong, D., Pei, D., Jin, X., & Liu, D. (2018). LncRNA CASC2 inhibits proliferation and migration of adenocarcinoma cells via miR-4735–3p and mTOR. Journal of Cellular Biochemistry, 120, 7506–7515.
Wang, S., Cao, F., Gu, X., Chen, J., Xu, R., Huang, Y., & Ying, L. (2019). LncRNA XIST, as a ceRNA of miR-204, aggravates lipopolysaccharide-induced acute respiratory distress syndrome in mice by upregulating IRF2. International Journal of Clinical and Experimental Pathology, 12(7), 2425–2434.
Du, B., Liu, M., Li, C., Geng, X., Zhang, X., Ning, D., & Liu, M. (2019). The potential role of TNFAIP3 in malignant transformation of gastric carcinoma. Pathology, Research and Practice, 215(8), 152471.
Hadisaputri, Y. E., Miyazaki, T., Yokobori, T., Sohda, M., Sakai, M., Ozawa, D., Hara, K., Honjo, H., Kumakura, Y., & Kuwano, H. (2017). TNFAIP3 overexpression is an independent factor for poor survival in esophageal squamous cell carcinoma. International Journal of Oncology, 50(3), 1002–1010.
Liu, K., Yao, H., Wen, Y., Zhao, H., Zhou, N., Lei, S., & Xiong, L. (2018). Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy. Biochimica et Biophysica Acta Molecular Basis of Disease, 1864(9 Pt B), 2871–2880.
Kanteti, R., Nallasura, V., Loganathan, S., Tretiakova, M., Kroll, T., Krishnaswamy, S., Faoro, L., Cagle, P., Husain, A. N., Vokes, E. E., & Lang, D. (2009). PAX5 is expressed in small-cell lung cancer and positively regulates c-Met transcription. Laboratory Investigation: A Journal of Technical Methods and Pathology, 89(3), 301–314.
Boudjadi, S., Chatterjee, B., Sun, W., Vemu, P., & Barr, F. G. (2018). The expression and function of PAX3 in development and disease. Gene, 666, 145–157.
Robson, E. J., He, S. J., & Eccles, M. R. (2006). A PANorama of PAX genes in cancer and development. Nature Reviews Cancer, 6(1), 52–62.
Liang, H., Li, G. L., Liu, J., Fu, M., Huang, H., Zhao, K., Wei, Y., & Xiao, J. (2021). The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer. Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 23(2), 283–288.
Zhang, N., Li, Z., Bai, F., & Zhang, S. (2019). PAX5-induced upregulation of IDH1-AS1 promotes tumor growth in prostate cancer by regulating ATG5-mediated autophagy. Cell Death & Disease, 10(10), 734.
Liu, S. L., Cai, C., Yang, Z. Y., Wu, Z. Y., Wu, X. S., Wang, X. F., Dong, P., & Gong, W. (2021). DGCR5 is activated by PAX5 and promotes pancreatic cancer via targeting miR-3163/TOP2A and activating Wnt/β-catenin pathway. International Journal of Biological Sciences, 17(2), 498–513.
Wang, W., Wang, Z., Wang, H., Li, X., & Wang, H. T. (2020). Promoting effect of PAX5-activated lncRNA UASR1 on growth of colorectal cancer by regulating the mTOR pathway. European Review for Medical and Pharmacological Sciences, 24(6), 2986–2993.
Funding
This work was supported by the National Natural Science Foundation of Zhejiang province, China (Y2100578 and Y2090486), Medical and health research project of Zhejiang Province, China (2017RC011), the Project of Medical and health science and technology of Hangzhou, China (B20220098), and the Project of Public welfare application research of Huzhou municipal science and Technology Bureau, China (2021GY44).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The original version of this article has been updated to due to open access cancellation.
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
Li, Y., Wu, Y., Dai, L. et al. Paired Box 5-Induced LINC00467 Upregulation Promotes the Progression of Laryngeal Squamous Cell Cancer by Triggering the MicroRNA-4735-3p/TNF Alpha-Induced Protein 3 Pathway. Mol Biotechnol 65, 655–667 (2023). https://doi.org/10.1007/s12033-022-00564-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12033-022-00564-3