Abstract
Circular RNAs (circRNAs) exhibit significant functions in diverse malignant tumors, including lung adenocarcinoma (LUAD). In this study, we aimed to elucidate the role of circRNA scm like with four mbt domains 2 (circSFMBT2) in LUAD. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay was performed for quantification of circSFMBT2, microRNA-1305 (miR-1305), spalt like transcription factor 4 (SALL4), proliferating Cell Nuclear Antigen (PCNA) or Ki-67. 5-ethynyl-2’-deoxyuridine (EdU) assay, transwell assay and flow cytometry analysis were applied to analyze cell proliferation, metastasis and apoptosis, respectively. Mouse xenograft model was established to explore the function of circSFMBT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to estimate the relationship between miR-1305 and circSFMBT2 or SALL4. CircSFMBT2 was upregulated in LUAD and related to advanced TNM stage and poor prognosis. CircSFMBT2 knockdown suppressed cell proliferation, metastasis, glycolysis and induced apoptosis in LUAD cells in vitro as well as tumor formation in vivo. CircSFMBT2 directly targeted miR-1305, and miR-1305 inhibition reversed circSFMBT2 knockdown-mediated inhibitory effects on LUAD malignant behaviors. SALL4 was the target gene of miR-1305. MiR-1305 overexpression repressed the malignant phenotypes of LUAD cells, while SALL4 enhancement abated the effects. CircSFMBT2 aggravated the progression of LUAD by the miR-1305/SALL4 axis, which might provide a diagnostic and prognostic marker for LUAD.
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References
Abdel-Wahab AF, Mahmoud W, Al-Harizy RM (2019) Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res 150:104511. https://doi.org/10.1016/j.phrs.2019.104511
Alexander M, Kim SY, Cheng H (2020) Update 2020: management of non-small cell lung cancer. Lung 198:897–907. https://doi.org/10.1007/s00408-020-00407-5
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Cai Y, Hao Y, Ren H, Dang Z, Xu H, Xue X, Gao Y (2019) miR-1305 inhibits the progression of non-small cell lung cancer by regulating MDM2. Cancer Manag Res 11:9529–9540. https://doi.org/10.2147/cmar.s220568
Cai X, Lin L, Zhang Q, Wu W, Su A (2020) Bioinformatics analysis of the circRNA-miRNA-mRNA network for non-small cell lung cancer. J Int Med Res 48:300060520929167. https://doi.org/10.1177/0300060520929167
Chang Z, Fu Y, Jia Y, Gao M, Song L, Zhang W, Zhao R, Qin Y (2021) Circ-SFMBT2 drives the malignant phenotypes of esophageal cancer by the miR-107-dependent regulation of SLC1A5. Cancer Cell Int 21:495. https://doi.org/10.1186/s12935-021-02156-8
Chang F, Li J, Sun Q, Wei S, Song Y (2022a) Hsa_circ_0017639 regulates cisplatin resistance and tumor growth via acting as a miR-1296-5p molecular sponge and modulating sine oculis homeobox 1 expression in non-small cell lung cancer. Bioengineered 13:8806–8822. https://doi.org/10.1080/21655979.2022.2053810
Chang W, Shang Z, Ming X, Wu J, Xiao Y (2022b) Circ-SFMBT2 facilitates the malignant growth of acute myeloid leukemia cells by modulating miR-582–3p/ZBTB20 pathway. Histol Histopathol 37:137–149. https://doi.org/10.14670/hh-18-398
Chen LL, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12:381–388. https://doi.org/10.1080/15476286.2015.1020271
Dou Y, Tian W, Wang H, Lv S (2021) Circ_0001944 contributes to glycolysis and tumor growth by upregulating NFAT5 through acting as a decoy for miR-142-5p in non-small cell lung cancer. Cancer Manag Res 13:3775–3787. https://doi.org/10.2147/CMAR.S302814
Gu R, Shao K, Xu Q, Zhao X, Qiu H, Hu H (2020) Circular RNA hsa_circ_0008003 facilitates tumorigenesis and development of non-small cell lung carcinoma via modulating miR-488/ZNF281 axis. J Cell Mol Med. https://doi.org/10.1111/jcmm.15987
Han Y, You J, Han Y, Liu Y, Huang M, Lu X, Chen J, Zheng Y (2021) LINC00184 promotes ovarian cancer cells proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305. Onco Targets Ther 14:2711–2726. https://doi.org/10.2147/OTT.S280490
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388. https://doi.org/10.1038/nature11993
Huang M, Li T, Wang Q, Li C, Zhou H, Deng S, Lv Z, He Y, Hou B, Zhu G (2021) Silencing circPVT1 enhances radiosensitivity in non-small cell lung cancer by sponging microRNA-1208. Cancer Biomark 31:263–279. https://doi.org/10.3233/cbm-203252
Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6:590–610. https://doi.org/10.1016/j.molonc.2012.09.006
Jiang X, Wang Z (2018) miR-16 targets SALL4 to repress the proliferation and migration of gastric cancer. Oncol Lett 16:3005–3012. https://doi.org/10.3892/ol.2018.8997
Jiang Z, Yin J, Peng G, Long X (2021) Circ_0074027 contributes to the progression of non-small cell lung cancer via microRNA-362-3p/clathrin heavy chain axis. Anticancer Drugs 32:1–10. https://doi.org/10.1097/CAD.0000000000000990
Lee YS, Dutta A (2009) MicroRNAs in cancer. Annu Rev Pathol 4:199–227. https://doi.org/10.1146/annurev.pathol.4.110807.092222
Li C, Zhang L, Meng G, Wang Q, Lv X, Zhang J, Li J (2019) Circular RNAs: pivotal molecular regulators and novel diagnostic and prognostic biomarkers in non-small cell lung cancer. J Cancer Res Clin Oncol 145:2875–2889. https://doi.org/10.1007/s00432-019-03045-4
Li B, Jin M, Cao F, Li J, Wu J, Xu L, Liu X, Shi Y, Chen W (2020a) Hsa_circ_0017639 expression promotes gastric cancer proliferation and metastasis by sponging miR-224-5p and upregulating USP3. Gene 750:144753. https://doi.org/10.1016/j.gene.2020.144753
Li J, Zhang G, Wu G (2020b) Effect of paeonol on proliferation, apoptosis, migration, invasion and glutamine of gastric cancer cells via circSFMBT2/miR-665 axis. Cell Mol Biol 66:33–40
Li X, Song L, Wang B, Tao C, Shi L, Xu M (2020c) Circ0120816 acts as an oncogene of esophageal squamous cell carcinoma by inhibiting miR-1305 and releasing TXNRD1. Cancer Cell Int 20:526. https://doi.org/10.1186/s12935-020-01617-w
Liu W, Xiao P, Wu H, Wang L, Kong D, Yu F (2017) MicroRNA-98 plays a suppressive role in non-small cell lung cancer through inhibition of SALL4 protein expression. Oncol Res 25:975–988. https://doi.org/10.3727/096504016X14791726591124
Liu W, Zhuang R, Feng S, Bai X, Jia Z, Kapora E, Tan W (2020) Long non-coding RNA ASB16-AS1 enhances cell proliferation, migration and invasion via functioning as a ceRNA through miR-1305/Wnt/beta-catenin axis in cervical cancer. Biomed Pharmacother 125:109965. https://doi.org/10.1016/j.biopha.2020.109965
Liu Y, Li C, Liu H, Wang J (2021) Circ_0001821 knockdown suppresses growth, metastasis, and TAX resistance of non-small-cell lung cancer cells by regulating the miR-526b-5p/GRK5 axis. Pharmacol Res Perspect 9:e00812. https://doi.org/10.1002/prp2.812
Ma Q, Huai B, Liu Y, Jia Z, Zhao Q (2021) Circular RNA circ_0020123 promotes non-small cell lung cancer progression through miR-384/TRIM44 axis. Cancer Manag Res 13:75–87. https://doi.org/10.2147/CMAR.S278913
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL (2019) Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 69:363–385. https://doi.org/10.3322/caac.21565
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83:584–594. https://doi.org/10.4065/83.5.584
Pezzuto A, D’Ascanio M, Ricci A, Pagliuca A, Carico E (2020) Expression and role of p16 and GLUT1 in malignant diseases and lung cancer: a review. Thorac Cancer 11:3060–3070. https://doi.org/10.1111/1759-7714.13651
Rodriguez E, Chen L, Ao MH, Geddes S, Gabrielson E, Askin F, Zhang H, Li QK (2014) Expression of transcript factors SALL4 and OCT4 in a subset of non-small cell lung carcinomas (NSCLC). Transl Respir Med 2:10. https://doi.org/10.1186/s40247-014-0010-7
Shangguan H, Feng H, Lv D, Wang J, Tian T, Wang X (2020) Circular RNA circSLC25A16 contributes to the glycolysis of non-small-cell lung cancer through epigenetic modification. Cell Death Dis 11:437. https://doi.org/10.1038/s41419-020-2635-5
Shi H, Huang S, Qin M, Xue X, Guo X, Jiang L, Hong H, Fang J, Gao L (2021a) Exosomal circ_0088300 derived from cancer-associated fibroblasts acts as a miR-1305 sponge and promotes gastric carcinoma cell tumorigenesis. Front Cell Dev Biol 9:676319. https://doi.org/10.3389/fcell.2021.676319
Shi J, Wang H, Feng W, Huang S, An J, Wang L, Jiang J (2021b) Hsa_circ_0069244 acts as the sponge of miR-346 to inhibit non-small cell lung cancer progression by regulating XPC expression. Hum Cell 34:1490–1503. https://doi.org/10.1007/s13577-021-00573-5
Su Y, Feng W, Shi J, Chen L, Huang J, Lin T (2020) circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-beta2/smad3 pathway. Mol Cancer 19:23. https://doi.org/10.1186/s12943-019-1129-5
Tafrihi M, Hasheminasab E (2019) MiRNAs: biology, biogenesis, their web-based tools, and databases. Microrna 8:4–27. https://doi.org/10.2174/2211536607666180827111633
Wang L, Shang X, Feng Q (2019) LncRNA TATDN1 contributes to the cisplatin resistance of non-small cell lung cancer through TATDN1/miR-451/TRIM66 axis. Cancer Biol Ther 20:261–271. https://doi.org/10.1080/15384047.2018.1529091
Xia Z, Qiu D, Deng J, Jiao X, Yang R, Sun Z, Wan X, Li J (2018) Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4. Int J Mol Med 41:2651–2659. https://doi.org/10.3892/ijmm.2018.3464
Xia H, Niu Q, Ding Y, Zhang Z, Yuan J, Jin W (2021) Long noncoding HOXA11-AS knockdown suppresses the progression of non-small cell lung cancer by regulating miR-3619-5p/SALL4 axis. J Mol Histol 52:729–740. https://doi.org/10.1007/s10735-021-09981-1
Yao J, Xu G, Zhu L, Zheng H (2020) circGFRA1 Enhances NSCLC progression by sponging miR-188-3p. Onco Targets Ther 13:549–558. https://doi.org/10.2147/ott.s230795
Yue Q, Xu Y, Deng X, Wang S, Qiu J, Qian B, Zhang Y (2021) Circ-PITX1 promotes the progression of non-small cell lung cancer through regulating the miR-1248/CCND2 axis. Onco Targets Ther 14:1807–1819. https://doi.org/10.2147/OTT.S286820
Zhang HD, Jiang LH, Sun DW, Hou JC, Ji ZL (2018) CircRNA: a novel type of biomarker for cancer. Breast Cancer 25:1–7. https://doi.org/10.1007/s12282-017-0793-9
Zhang Y, Yao H, Li Y, Yang L, Zhang L, Chen J, Wang Y, Li X (2021) Circular RNA TADA2A promotes proliferation and migration via modulating of miR638/KIAA0101 signal in nonsmall cell lung cancer. Oncol Rep. https://doi.org/10.3892/or.2021.8152
Zhang HB, Qiu XM, Zhang YC, Huang TT, Zuo ZJ, Zhang T (2022) Circ_0017639 facilitates proliferative, migratory, and invasive potential of non-small cell lung cancer (NSCLC) cells via PI3K/AKT signaling pathway. Bioengineered 13:1590–1601. https://doi.org/10.1080/21655979.2021.2020390
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XZ was responsible for drafting the manuscript. XX, YW contributed to the analysis and interpretation of data. XZ, XX contributed in the data collection. All authors read and approved the final manuscript.
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Zhao, X., Xing, X. & Wu, Y. CircSFMBT2 Plays an Oncogenic Role in Lung Adenocarcinoma Depending on the miR-1305/SALL4 Axis. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10611-6
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DOI: https://doi.org/10.1007/s10528-023-10611-6