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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

BBOX1-AS1 Activates Hedgehog Signaling Pathway to Facilitate the Proliferation and Stemness of Esophageal Squamous Cell Carcinoma Cells via miR-506-5p/EIF5A/PTCH1 Axis

Author(s): Liya Hu, Hong Cao, Lijun Zheng and Ruichao Li*

Volume 16, Issue 8, 2023

Published on: 31 March, 2023

Article ID: e300123213257 Pages: 11

DOI: 10.2174/1874467216666230130132927

Price: $65

Abstract

Aims and Objective: This study aimed to unveil the specific function of lncRNA BBOX1 antisense RNA 1 (BBOX1-AS1) in ESCC cells and the underlying regulatory mechanism.

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly disease. Molecular mechanisms essential to ESCC development and progression require in-depth investigation. Long noncoding RNAs (lncRNAs) have been suggested as crucial effectors in modulating tumor growth.

Methods: RT-qPCR and western blot examined the expression of genes and proteins of concern, respectively. Colony formation and EdU assays assessed the changes in cell proliferation. Sphere formation assay also detected the stemness of ESCC cells. Bioinformatics prediction, along with mechanistic assays (FISH, Subcellular fractionation, RNA pull-down, RIP, and luciferase reporter), was conducted to explore the gene interactions and regulatory relationship.

Results: BBOX1-AS1 was observed to be aberrantly up-regulated in ESCC tissues and cell lines. BBOX1-AS1 depletion exerted suppressive impacts on ESCC cell proliferation and stemness, while BBOX1-AS1 overexpression led to the opposite consequences. Moreover, BBOX1-AS1 was verified to activate Hedgehog signaling pathway via up-regulating PTCH1, and BBOX1-AS1 could sponge miR-506-5p to up-regulate EIF5A, thus stabilizing PTCH1 mRNA. Rescue experiments indicated that BBOX1-AS1 could affect ESCC cell proliferation and stemness via modulation on PTCH1.

Conclusion: To conclude, BBOX1-AS1 activates Hedgehog signaling pathway to facilitate the proliferation and stemness of ESCC cells via miR-506-5p/EIF5A/PTCH1 axis.

Graphical Abstract

[1]
Yan, J.; Shi, L.; Lin, S.; Li, Y. MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell re-sistance to cisplatin and paclitaxel. Bioengineered, 2021, 12(1), 5334-5347.
[http://dx.doi.org/10.1080/21655979.2021.1938497] [PMID: 34415232]
[2]
Liu, B.; Li, X.; Li, C.; Xu, R.; Sun, X. miR-25 mediates metastasis and epithelial–mesenchymal-transition in human esophageal squamous cell carcinoma via regulation of E-cadherin signaling. Bioengineered, 2019, 10(1), 679-688.
[http://dx.doi.org/10.1080/21655979.2019.1687391] [PMID: 31679450]
[3]
Shi, J.; Fu, C.; Su, X.; Feng, S.; Wang, S. Ultrasound-stimulated microbubbles inhibit aggressive phenotypes and promotes radiosensitivity of esophageal squamous cell carcinoma. Bioengineered, 2021, 12(1), 3000-3013.
[http://dx.doi.org/10.1080/21655979.2021.1931641] [PMID: 34180353]
[4]
Xu, J.; Wang, J.; Liu, L.; Chen, L.; Hu, S.; Liu, F. MicroRNA -196b is related to the overall survival of patients with esophageal squamous cell carcinoma and facilitates tumor progression by regulating SOCS2 (Suppressor Of Cytokine Signaling 2). Bioengineered, 2021, 12(1), 7737-7746.
[http://dx.doi.org/10.1080/21655979.2021.1982329] [PMID: 34605350]
[5]
Yang, L.; Lu, P.; Yang, X.; Li, K.; Chen, X.; Qu, S. Excavating novel diagnostic and prognostic long non-coding RNAs (lncRNAs) for head and neck squamous cell carcinoma: an integrated bioinformatics analysis of competing endogenous RNAs (ceRNAs) and gene co-expression networks. Bioengineered, 2021, 12(2), 12821-12838.
[http://dx.doi.org/10.1080/21655979.2021.2003925] [PMID: 34898376]
[6]
Fu, X.; Chen, X.; Si, Y.; Yao, Y.; Jiang, Z.; Chen, K. Long non-coding RNA NCK1-AS1 is overexpressed in esophageal squamous cell car-cinoma and predicts survival. Bioengineered, 2022, 13(4), 8302-8310.
[http://dx.doi.org/10.1080/21655979.2022.2038449] [PMID: 35311444]
[7]
Guo, Y.; Sun, P.; Guo, W.; Yin, Q.; Han, J.; Sheng, S.; Liang, J.; Dong, Z. LncRNA DDX11 antisense RNA 1 promotes EMT process of esophageal squamous cell carcinoma by sponging miR-30d-5p to regulate SNAI1/ZEB2 expression and Wnt/β-catenin pathway. Bioengineered, 2021, 12(2), 11425-11440.
[http://dx.doi.org/10.1080/21655979.2021.2008759] [PMID: 34866524]
[8]
Jiang, H.; He, Q.; Liu, T. BBOX1-AS1 accelerates nasopharyngeal carcinoma progression by sponging miR-3940-3p and enhancing KPNA2 upregulation. Cancer Manag. Res., 2021, 13, 9049-9062.
[http://dx.doi.org/10.2147/CMAR.S327211] [PMID: 34938119]
[9]
Liu, J.; Zhu, J.; Xiao, Z.; Wang, X.; Luo, J. BBOX1‐AS1 contributes to colorectal cancer progression by sponging hsa‐ miR‐361‐3p and targeting SH2B1. FEBS Open Bio, 2022, 12(5), 983-992.
[http://dx.doi.org/10.1002/2211-5463.12802] [PMID: 31984680]
[10]
Tang, S.; Wang, Y.; Xie, G.; Li, W.; Chen, Y.; Liang, J.; Liu, P.; Song, F.; Zhou, J. Regulation of Ptch1 by miR-342-5p and FoxO3 Induced Autophagy Involved in Renal Fibrosis. Front. Bioeng. Biotechnol., 2020, 8, 583318.
[http://dx.doi.org/10.3389/fbioe.2020.583318] [PMID: 33251198]
[11]
Yang, L.; Xu, X.; Chen, Z.; Zhang, Y.; Chen, H.; Wang, X. miR-511-3p promotes hepatic sinusoidal obstruction syndrome by activating hedgehog pathway via targeting Ptch1. Am. J. Physiol. Gastrointest. Liver Physiol., 2021, 321(3), G344-G354.
[http://dx.doi.org/10.1152/ajpgi.00081.2021] [PMID: 34287088]
[12]
Xu, H.; Sun, X.; Huang, Y.; Si, Q.; Li, M. Long non coding RNA NEAT1 modifies cell proliferation, colony formation, apoptosis, migration and invasion via the miR 4500/BZW1 axis in ovarian cancer. Mol. Med. Rep., 2020, 22(4), 3347-3357.
[http://dx.doi.org/10.3892/mmr.2020.11408] [PMID: 32945505]
[13]
Zeng, K.; Chen, X.; Xu, M.; Liu, X.; Hu, X.; Xu, T.; Sun, H.; Pan, Y.; He, B.; Wang, S. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis., 2018, 9(4), 417.
[http://dx.doi.org/10.1038/s41419-018-0454-8] [PMID: 29549306]
[14]
Ding, D.; Yang, F.; Chen, Z.; Ying, J. Circ_0007385 regulates cell proliferation, apoptosis and stemness via targeting MIR ‐493‐3p/RAB22A axis in non‐small cell lung cancer. Thorac. Cancer, 2022, 13(4), 571-581.
[http://dx.doi.org/10.1111/1759-7714.14300] [PMID: 34989145]
[15]
Jian, F.; Che, X.; Zhang, J.; Liu, C.; Liu, G.; Tang, Y.; Feng, W. The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer pro-gression by regulating AURKA degradation. Cell Death Dis., 2021, 12(4), 351.
[http://dx.doi.org/10.1038/s41419-021-03595-x] [PMID: 33824269]
[16]
Ye, G.; Zhang, Z.; Zhu, C.; Cong, Z.; Cui, Z.; Chen, L.; Zhao, G. Long Non-Coding RNA LINC01569 Promotes Proliferation and Metastasis in Colorectal Cancer by miR-381-3p/RAP2A Axis. Front. Oncol., 2021, 11, 727698.
[http://dx.doi.org/10.3389/fonc.2021.727698] [PMID: 34422671]
[17]
Rao, M.; Xu, S.; Zhang, Y.; Liu, Y.; Luan, W.; Zhou, J. Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metas-tasis by sponging miR-497-5p to regulate HMGA2 expression. Cell Death Dis., 2021, 12(10), 859.
[http://dx.doi.org/10.1038/s41419-021-04123-7] [PMID: 34552050]
[18]
Tang, S.; Xie, Z.; Wang, P.; Li, J.; Wang, S.; Liu, W.; Li, M.; Wu, X.; Su, H.; Cen, S.; Ye, G.; Zheng, G.; Wu, Y.; Shen, H. LncRNA-OG pro-motes the osteogenic differentiation of bone marrow-derived mesenchymal stem cells under the regulation of hnRNPK. Stem Cells, 2019, 37(2), 270-283.
[http://dx.doi.org/10.1002/stem.2937] [PMID: 30372559]
[19]
Li, Y.; Jiang, A. ST8SIA6-AS1 promotes hepatocellular carcinoma by absorbing miR-5195-3p to regulate HOXB6. Cancer Biol. Ther., 2020, 21(7), 647-655.
[http://dx.doi.org/10.1080/15384047.2020.1743150] [PMID: 32420798]
[20]
Jackstadt, R.; van Hooff, S.R.; Leach, J.D.; Cortes-Lavaud, X.; Lohuis, J.O.; Ridgway, R.A.; Wouters, V.M.; Roper, J.; Kendall, T.J.; Rox-burgh, C.S.; Horgan, P.G.; Nixon, C.; Nourse, C.; Gunzer, M.; Clark, W.; Hedley, A.; Yilmaz, O.H.; Rashid, M.; Bailey, P.; Biankin, A.V.; Campbell, A.D.; Adams, D.J.; Barry, S.T.; Steele, C.W.; Medema, J.P.; Sansom, O.J. Epithelial NOTCH signaling rewires the tumor microen-vironment of colorectal cancer to drive poor-prognosis subtypes and metastasis. Cancer Cell, 2019, 36(3), 319-336.e7.
[http://dx.doi.org/10.1016/j.ccell.2019.08.003] [PMID: 31526760]
[21]
Skoda, A.M.; Simovic, D.; Karin, V.; Kardum, V.; Vranic, S.; Serman, L. The role of the Hedgehog signaling pathway in cancer: A compre-hensive review. Bosn. J. Basic Med. Sci., 2018, 18(1), 8-20.
[http://dx.doi.org/10.17305/bjbms.2018.2756] [PMID: 29274272]
[22]
Zhang, H.; Fang, Z.; Guo, Y.; Wang, D. Long noncoding RNA SNHG10 promotes colorectal cancer cells malignant progression by targeting miR-3690. Bioengineered, 2021, 12(1), 6010-6020.
[http://dx.doi.org/10.1080/21655979.2021.1972199] [PMID: 34477483]
[23]
Xu, R.; Zhang, X.; Xu, Y.; Wang, J.; Li, Z.; Cui, X. Long noncoding RNA MST1P2 promotes cervical cancer progression by sponging with microRNA miR-133b. Bioengineered, 2021, 12(1), 1851-1860.
[http://dx.doi.org/10.1080/21655979.2021.1921550] [PMID: 34034626]
[24]
Li, Z.; Sun, C.; Chen, M.; Wang, B. Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression. Bioengineered, 2021, 12(1), 6891-6901.
[http://dx.doi.org/10.1080/21655979.2021.1973781] [PMID: 34516336]
[25]
Xu, J.; Yang, B.; Wang, L.; Zhu, Y.; Zhu, X.; Xia, Z.; Zhao, Z.; Xu, L. LncRNA BBOX1‐AS1 upregulates HOXC6 expression through miR‐361‐3p and HuR to drive cervical cancer progression. Cell Prolif., 2020, 53(7), e12823.
[http://dx.doi.org/10.1111/cpr.12823] [PMID: 32515533]
[26]
Shi, J.; Yang, C.; An, J.; Hao, D.; Liu, C.; Liu, J.; Sun, J.; Jiang, J. KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway. J. Exp. Clin. Cancer Res., 2021, 40(1), 148.
[http://dx.doi.org/10.1186/s13046-021-01943-5] [PMID: 33931086]
[27]
Zhang, H.; Liu, S.; Tang, L.; Ge, J.; Lu, X. Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/β-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9). Bioengineered, 2021, 12(1), 162-171.
[http://dx.doi.org/10.1080/21655979.2020.1863014] [PMID: 33356805]
[28]
Ding, X.; Xu, X.; He, X.F.; Yuan, Y.; Chen, C.; Shen, X.Y.; Su, S.; Chen, Z.; Xu, S.T.; Huang, Y.H. Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR sig-naling. Bioengineered, 2021, 12(1), 803-814.
[http://dx.doi.org/10.1080/21655979.2021.1890383] [PMID: 33648424]
[29]
Wang, H.; Di, X.; Bi, Y.; Sun, S.; Wang, T. Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p. Bioengineered, 2021, 12(1), 1791-1802.
[http://dx.doi.org/10.1080/21655979.2021.1924554] [PMID: 33975517]
[30]
Liu, X.; Yin, Z.; Xu, L.; Liu, H.; Jiang, L.; Liu, S.; Sun, X. Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway. Cell Death Dis., 2021, 12(2), 173.
[http://dx.doi.org/10.1038/s41419-021-03435-y] [PMID: 33568633]
[31]
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]
[32]
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. LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Mol. Cancer, 2018, 17(1), 126.
[http://dx.doi.org/10.1186/s12943-018-0874-1] [PMID: 30134915]

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