lncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer
Lanfen An
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Search for more papers by this authorKejun Dong
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorShuqi Chi
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China
Search for more papers by this authorSitian Wei
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorJun Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZhicheng Yu
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorQian Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorTangansu Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorShuangshuang Cheng
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorRui Shi
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZhishan Jin
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorXing Zhou
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYingchao Zhao
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCorresponding Author
Hongbo Wang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence Hongbo Wang, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
Email: [email protected]
Search for more papers by this authorLanfen An
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Plastic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Search for more papers by this authorKejun Dong
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorShuqi Chi
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China
Search for more papers by this authorSitian Wei
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorJun Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZhicheng Yu
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorQian Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorTangansu Zhang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorShuangshuang Cheng
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorRui Shi
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorZhishan Jin
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorXing Zhou
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorYingchao Zhao
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCorresponding Author
Hongbo Wang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence Hongbo Wang, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 Wuhan, China.
Email: [email protected]
Search for more papers by this authorAbstract
Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are available in the supplementary material of this article Data are available upon reasonable request. The readers can consult the first author (email: [email protected]).
Supporting Information
Filename | Description |
---|---|
mc23659-sup-0001-Table_S1_Different_expressions_of_genes.xls391.3 KB | Supporting information. |
mc23659-sup-0002-Table_S2_11_lncRNAs_upregulated_in_CC_samples.xlsx9.3 KB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71: 209-249. doi:10.3322/caac.21660
- 2Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66: 115-132. doi:10.3322/caac.21338
- 3Wentzensen N, Schiffman M. Accelerating cervical cancer control and prevention. Lancet Public Health. 2018; 3: e6-e7. doi:10.1016/S2468-2667(17)30242-6
- 4Tsikouras P, Zervoudis S, Manav B, et al. Cervical cancer: screening, diagnosis and staging. J BUON: Off J Balkan Union Oncol. 2016; 21: 320-325.
- 5Brucker SY, Ulrich UA. Surgical treatment of early-stage cervical cancer. Oncol Res Treat. 2016; 39: 508-514. doi:10.1159/000448794
- 6Sun Z, Liu J, Chen C, et al. The biological effect and clinical application of long noncoding RNAs in colorectal cancer. Cell Physiol Biochem. 2018; 46: 431-441. doi:10.1159/000488610
- 7Cipolla G, de Oliveira J, Salviano-Silva A, et al. Long non-coding RNAs in multifactorial diseases: another layer of complexity. Non-Coding RNA. 2018; 4:13. doi:10.3390/ncrna4020013
- 8Evans JR, Feng FY, Chinnaiyan AM. The bright side of dark matter: lncRNAs in cancer. J Clin Invest. 2016; 126: 2775-2782. doi:10.1172/JCI84421
- 9de Oliveira JC, Oliveira LC, Mathias C, et al. Long non-coding RNAs in cancer: another layer of complexity. J Gene Med. 2019; 21:e3065. doi:10.1002/jgm.3065
- 10Shang C, Wang W, Liao Y, et al. LNMICC promotes nodal metastasis of cervical cancer by reprogramming fatty acid metabolism. Cancer Res. 2018; 78: 877-890. doi:10.1158/0008-5472.CAN-17-2356
- 11Chen C, Shen N, Chen Y, et al. LncCCLM inhibits lymphatic metastasis of cervical cancer by promoting STAU1-mediated IGF-1 mRNA degradation. Cancer Lett. 2021; 518: 169-179. doi:10.1016/j.canlet.2021.07.005
- 12Wang XS, Zhang Z, Wang HC, et al. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 2006; 12: 4851-4858. doi:10.1158/1078-0432.CCR-06-0134
- 13Tsang WP, Wong TWL, Cheung AHH, Co CNN, Kwok TT. Induction of drug resistance and transformation in human cancer cells by the noncoding RNACUDR. RNA. 2007; 13: 890-898. doi:10.1261/rna.359007
- 14Kadoch C, Hargreaves DC, Hodges C, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013; 45: 592-601. doi:10.1038/ng.2628
- 15Mittal P, Roberts CWM. The SWI/SNF complex in cancer—biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020; 17: 435-448. doi:10.1038/s41571-020-0357-3
- 16Tropée R, de la Peña Avalos B, Gough M, Snell C, Duijf PHG, Dray E. The SWI/SNF subunit SMARCD3 regulates cell cycle progression and predicts survival outcome in ER+ breast cancer. Breast Cancer Res Treat. 2021; 185: 601-614. doi:10.1007/s10549-020-05997-5
- 17Jiang M, Wang H, Chen H, Han Y. SMARCD3 is a potential prognostic marker and therapeutic target in CAFs. Aging. 2020; 12: 20835-20861. doi:10.18632/aging.104102
- 18Sun X, Hota SK, Zhou YQ, et al. Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function. Biol Open. 2018; 7(1):bio029512. doi:10.1242/bio.029512
- 19He F, Shu Y, Wang X, et al. Intensive glucose control reduces the risk effect of TRIB3, SMARCD3, and ATF6 genetic variation on diabetic vascular complications. Front Pharmacol. 2018; 9:1422. doi:10.3389/fphar.2018.01422
- 20Kok VC, Yu CC. Cancer-derived exosomes: their role in cancer biology and biomarker development. Int J Nanomed. 2020; 15: 8019-8036. doi:10.2147/IJN.S272378
- 21Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer. 2022; 21: 25. doi:10.1186/s12943-022-01505-z
- 22An L, Zhang J, Feng D, et al. KIF2C is a novel prognostic biomarker and correlated with immune infiltration in endometrial cancer. Stem Cells Int. 2021; 2021: 1-13. doi:10.1155/2021/1434856
- 23Lobb RJ, Becker M, Wen Wen S, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles. 2015; 4:27031. doi:10.3402/jev.v4.27031
- 24Wang H, Zhao Y, Chen M, Cui J. Identification of novel long non-coding and circular RNAs in human papillomavirus-mediated cervical cancer. Front Microbiol. 2017; 8:1720. doi:10.3389/fmicb.2017.01720
- 25Jiang H, Li T, Qu Y, et al. Long non-coding RNA SNHG15 interacts with and stabilizes transcription factor Slug and promotes colon cancer progression. Cancer Lett. 2018; 425: 78-87. doi:10.1016/j.canlet.2018.03.038
- 26Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription? Sci Adv. 2017; 3:o2110. doi:10.1126/sciadv.aao2110
- 27Hentze MW, Castello A, Schwarzl T, Preiss T. A brave new world of RNA-binding proteins. Nat Rev Mol Cell Biol. 2018; 19: 327-341. doi:10.1038/nrm.2017.130
- 28Wang ZQ, Cai Q, Hu L, et al. Long noncoding RNA UCA1 induced by SP1 promotes cell proliferation via recruiting EZH2 and activating AKT pathway in gastric cancer. Cell Death Dis. 2017; 8:e2839. doi:10.1038/cddis.2017.143
- 29Jordan NV, Prat A, Abell AN, et al. SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c controls epithelial-mesenchymal transition by inducing Wnt5a signaling. Mol Cell Biol. 2013; 33: 3011-3025. doi:10.1128/MCB.01443-12
- 30Kim EJ, Liu P, Zhang S, et al. BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity. Nucleic Acids Res. 2021; 49: 12211-12233. doi:10.1093/nar/gkab1122
- 31Qin Y, Hou Y, Liu S, et al. A novel long non-coding RNA lnc030 maintains breast cancer stem cell stemness by stabilizing SQLE mRNA and increasing cholesterol synthesis. Adv Sci. 2022; 9:2204046. doi:10.1002/advs.202204046
10.1002/advs.202204046 Google Scholar
- 32Bartl J, Zanini M, Bernardi F, et al. The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors. Nat Commun. 2022; 13: 4061. doi:10.1038/s41467-022-31574-z
- 33Zhang Q, Xiu B, Zhang L, et al. Immunosuppressive lncRNA LINC00624 promotes tumor progression and therapy resistance through ADAR1 stabilization. J Immunother Cancer. 2022; 10:e004666. doi:10.1136/jitc-2022-004666
- 34Zang X, Gu J, Zhang J, et al. Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression. Cell Death Dis. 2020; 11: 215. doi:10.1038/s41419-020-2409-0
- 35Yang L, Peng X, Li Y, et al. Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma. Mol Cancer. 2019; 18: 78. doi:10.1186/s12943-019-0990-6
- 36Ni C, Fang QQ, Chen WZ, et al. Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells. Signal Transduct Target Ther. 2020; 5: 41. doi:10.1038/s41392-020-0129-7
- 37Zhou X, Zhong F, Yan Y, et al. Pancreatic cancer cell-derived exosomes promote lymphangiogenesis by downregulating ABHD11-AS1 expression. Cancers. 2022; 14:4612. doi:10.3390/cancers14194612
- 38Shen T, Miao S, Zhou Y, et al. Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3. Cell Commun Signaling. 2022; 20: 152. doi:10.1186/s12964-022-00957-6
- 39Li L, Huang L, Huang C, et al. The multiomics landscape of serum exosomes during the development of sepsis. J Adv Res. 2022; 39: 203-223. doi:10.1016/j.jare.2021.11.005
- 40Guo X, Lv X, Ru Y, et al. Circulating exosomal gastric cancer-associated long noncoding RNA1 as a biomarker for early detection and monitoring progression of gastric cancer. JAMA Surgery. 2020; 155: 572. doi:10.1001/jamasurg.2020.1133
- 41Chen C, Luo Y, He W, et al. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. J Clin Invest. 2020; 130: 404-421. doi:10.1172/JCI130892
- 42Zhang X, Wang W, Zhu W, et al. Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int J Mol Sci. 2019; 20:5573. doi:10.3390/ijms20225573
- 43Yang Z, Zhang H, Yin M, et al. TGF-β1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a. J Mol Med (Berlin, Germany). 2022; 100: 1465-1478. doi:10.1007/s00109-022-02248-6
- 44Yang G, Tian Y, Li C, et al. LncRNA UCA1 regulates silicosis-related lung epithelial cell-to-mesenchymal transition through competitive adsorption of miR-204-5p. Toxicol Appl Pharmacol. 2022; 441:115977. doi:10.1016/j.taap.2022.115977
- 45Yang A, Liu X, Liu P, et al. LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis. Cell Mol Biol Lett. 2021; 26: 33. doi:10.1186/s11658-021-00275-8
- 46An M, Xing X, Chen T. Long non-coding RNA UCA1 enhances cervical cancer cell proliferation and invasion by regulating microRNA-299-3p expression. Oncol Lett. 2021; 22: 772. doi:10.3892/ol.2021.13033
- 47Chen MH, Qi B, Cai QQ, et al. LncRNA lncAY is upregulated by sulfatide via Myb/MEF2C acetylation to promote the tumorigenicity of hepatocellular carcinoma cells. Biochim Biophys Acta (BBA)—Gene Regul Mech. 2022; 1865:194777. doi:10.1016/j.bbagrm.2021.194777
- 48Zhang M, Wang J, Jin Y, et al. YTHDF2-mediated FGF14-AS2 decay promotes osteolytic metastasis of breast cancer by enhancing RUNX2 mRNA translation. Br J Cancer. 2022; 127: 2141-2153. doi:10.1038/s41416-022-02006-y
- 49Huang G, Xiang Z, Wu H, et al. The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination. Int J Biol Sci. 2022; 18: 1415-1433. doi:10.7150/ijbs.69454
- 50Wang Y, Wong RHF, Tang T, et al. Phosphorylation and recruitment of BAF60c in chromatin remodeling for lipogenesis in response to insulin. Mol Cell. 2013; 49: 283-297. doi:10.1016/j.molcel.2012.10.028
- 51Ajore R, Niroula A, Pertesi M, et al. Functional dissection of inherited non-coding variation influencing multiple myeloma risk. Nat Commun. 2022; 13: 151. doi:10.1038/s41467-021-27666-x
- 52Lan J, Wei G, Liu J, Yang F, Sun R, Lu H. Chemotherapy-induced adenosine A2B receptor expression mediates epigenetic regulation of pluripotency factors and promotes breast cancer stemness. Theranostics. 2022; 12: 2598-2612. doi:10.7150/thno.70581
- 53Lickert H, Takeuchi JK, von Both I, et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature. 2004; 432: 107-112. doi:10.1038/nature03071
- 54Tsering T, Li M, Chen Y, et al. EV-ADD, a database for EV-associated DNA in human liquid biopsy samples. J Extracell Vesicles. 2022; 11:e12270. doi:10.1002/jev2.12270
- 55Wu T, Liu Y, Cao Y, Liu Z. Engineering macrophage exosome disguised biodegradable nanoplatform for enhanced sonodynamic therapy of glioblastoma. Adv Mater. 2022; 34:2110364. doi:10.1002/adma.202110364
- 56Zhang Q, Deng T, Zhang H, et al. Adipocyte-derived exosomal MTTP suppresses ferroptosis and promotes chemoresistance in colorectal cancer. Adv Sci. 2022; 9:2203357. doi:10.1002/advs.202203357