LINC00649 promotes bladder cancer malignant progression by regulating the miR‑15a‑5p/HMGA1 axis

Chen,Xuanyu; Chen,Song

doi:10.3892/or.2021.7959

LINC00649 promotes bladder cancer malignant progression by regulating the miR‑15a‑5p/HMGA1 axis

Authors:
- Xuanyu Chen
- Song Chen
View Affiliations

Affiliations: Department of Urology, The First People's Hospital of Wenling, Wenling, Zhejiang 317500, P.R. China
Published online on: February 1, 2021 https://doi.org/10.3892/or.2021.7959
Article Number: 8
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to explore the effects of LINC00649 on the proliferation, migration and invasion of bladder cancer (BC) and identify possible mechanisms. Through TCGA database analysis of LINC00649 expression in bladder cancer and the association of LINC00649 with the BC patient prognosis, RT‑qPCR was employed for detecting LINC00649 expression in 60 clinical tissue specimens and cell lines of bladder cancer. The lentivirus stable transfection or small interfering RNA was used to increase or decrease the LINC00649 expression level in T24 and UM‑UC‑3 cells. CCK8 and clone formation assay were utilized to observe the effects of LINC00649 on the proliferation and colony formation of BC cells. Transwell experiment was performed to detect the effects of LINC00649 on the migration and invasion of bladder cancer. Bioinformatics database was used to identify the possible downstream targets of LINC00649 while RT‑qPCR, western blot analysis and dual luciferase reporter gene experiments were carried out to verify the possible molecular mechanism. The TCGA database analysis revealed a significantly high expression of LINC00649 in bladder cancer and an association of LINC00649 expression with overall survival rate of BC patients. As shown by RT‑qPCR detection, LINC00649 expression was notably upregulated in BC tissues and BC cell lines. In addition, statistical analyses unveiled that highly expressed LINC00649 was clearly associated with poor overall survival of bladder cancer. Based on the in vitro cell experiment, upregulated LINC00649 considerately enhanced the proliferation, migration and invasion of BC cells, as opposed to those in T24 and UM‑UC‑3 cells by suppressing LINC00649. Mechanically, LINC00649 may promote the malignant progression of bladder cancer by regulating miR‑15a‑5p to promote the HMGA1 expression axis. Overall, LINC00649 upregulates HMGA1 expression by binding to miR‑15a‑5p to enhance the proliferation, migration and invasion of BC cells. Thus, LINC00649 is a potential biomarker and therapeutic target for bladder cancer.

View Figures

View References

1	Afonso J, Santos LL, Longatto-Filho A and Baltazar F: Competitive glucose metabolism as a target to boost bladder cancer immunotherapy. Nat Rev Urol. 17:77–106. 2020. View Article : Google Scholar : PubMed/NCBI
2	Alifrangis C, McGovern U, Freeman A, Powles T and Linch M: Molecular and histopathology directed therapy for advanced bladder cancer. Nat Rev Urol. 16:465–483. 2019. View Article : Google Scholar : PubMed/NCBI
3	Meng MV, Gschwend JE, Shore N, Grossfeld GD, Mostafid H and Black PC: Emerging immunotherapy options for bacillus calmette-guerin unresponsive nonmuscle invasive bladder cancer. J Urol. 202:1111–1119. 2019. View Article : Google Scholar : PubMed/NCBI
4	Soria F, D'Andrea D, Pohar K, Shariat SF and Lotan Y: Diagnostic, prognostic and surveillance urinary markers in nonmuscle invasive bladder cancer: Any role in clinical practice? Curr Opin Urol. 28:577–583. 2018. View Article : Google Scholar : PubMed/NCBI
5	Dobruch J, Daneshmand S, Fisch M, Lotan Y, Noon AP, Resnick MJ, Shariat SF, Zlotta AR and Boorjian SA: Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes. Eur Urol. 69:300–310. 2016. View Article : Google Scholar : PubMed/NCBI
6	Guo X and Hua Y: CCAT1: An oncogenic long noncoding RNA in human cancers. J Cancer Res Clin Oncol. 143:555–562. 2017. View Article : Google Scholar : PubMed/NCBI
7	Zhang X, Hamblin MH and Yin KJ: The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 14:1705–1714. 2017. View Article : Google Scholar : PubMed/NCBI
8	Chen LL: Linking long noncoding RNA localization and function. Trends Biochem Sci. 41:761–772. 2016. View Article : Google Scholar : PubMed/NCBI
9	Sallam T, Sandhu J and Tontonoz P: Long noncoding RNA discovery in cardiovascular disease: Decoding form to function. Circ Res. 122:155–166. 2018. View Article : Google Scholar : PubMed/NCBI
10	Wang Y, Chen F, Zhao M, Yang Z, Li J, Zhang S, Zhang W, Ye L and Zhang X: The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186. J Biol Chem. 292:15395–15407. 2017. View Article : Google Scholar : PubMed/NCBI
11	Chen S, Chen JZ, Zhang JQ, Chen HX, Qiu FN, Yan ML, Tian YF, Peng CH, Shen BY, Chen YL and Wang YD: Silencing of long noncoding RNA LINC00958 prevents tumor initiation of pancreatic cancer by acting as a sponge of microRNA-330-5p to down-regulate PAX8. Cancer Lett. 446:49–61. 2019. View Article : Google Scholar : PubMed/NCBI
12	Lu Q, Shan S, Li Y, Zhu D, Jin W and Ren T: Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p. FASEB J. 32:3957–3967. 2018. View Article : Google Scholar : PubMed/NCBI
13	Wang M, Guo C, Wang L, Luo G, Huang C, Li Y, Liu D, Zeng F, Jiang G and Xiao X: Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription. Cell Death Dis. 9:2382018. View Article : Google Scholar : PubMed/NCBI
14	Liu Z, Xie D and Zhang H: Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis. Cell Death Dis. 9:10422018. View Article : Google Scholar : PubMed/NCBI
15	Soukup V, Capoun O, Cohen D, Hernandez V, Babjuk M, Burger M, Compérat E, Gontero P, Lam T, MacLennan S, et al: Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health organization grading classification systems in non-muscle-invasive bladder cancer: A european association of urology non-muscle invasive bladder cancer guidelines panel systematic review. Eur Urol. 72:801–813. 2017. View Article : Google Scholar : PubMed/NCBI
16	Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A and Bray F: Bladder cancer incidence and mortality: A global overview and recent trends. Eur Urol. 71:96–108. 2017. View Article : Google Scholar : PubMed/NCBI
17	Lobo N, Mount C, Omar K, Nair R, Thurairaja R and Khan MS: Landmarks in the treatment of muscle-invasive bladder cancer. Nat Rev Urol. 14:565–574. 2017. View Article : Google Scholar : PubMed/NCBI
18	Lin C and Yang L: Long noncoding RNA in cancer: Wiring signaling circuitry. Trends Cell Biol. 28:287–301. 2018. View Article : Google Scholar : PubMed/NCBI
19	Chen M, Li J, Zhuang C and Cai Z: Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer. Oncotarget. 8:28176–28186. 2017. View Article : Google Scholar : PubMed/NCBI
20	Chen M, Zhuang C, Liu Y, Li J, Dai F, Xia M, Zhan Y, Lin J, Chen Z, He A, et al: Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer. Cancer Lett. 376:155–164. 2016. View Article : Google Scholar : PubMed/NCBI
21	Feng F, Chen A, Huang J, Xia Q, Chen Y and Jin X: Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/β-catenin pathway axis. J Cell Biochem. 119:9408–9418. 2018. View Article : Google Scholar : PubMed/NCBI
22	Schmitz SU, Grote P and Herrmann BG: Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 73:2491–2509. 2016. View Article : Google Scholar : PubMed/NCBI
23	Jandura A and Krause HM: The New RNA World: Growing Evidence for Long Noncoding RNA Functionality. Trends Genet. 33:665–676. 2017. View Article : Google Scholar : PubMed/NCBI
24	Fu F, Wang T, Wu Z, Feng Y, Wang W, Zhou S, Ma X and Wang S: HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer. Cell Death Dis. 9:5942018. View Article : Google Scholar : PubMed/NCBI
25	Zanin R, Pegoraro S, Ros G, Ciani Y, Piazza S, Bossi F, Bulla R, Zennaro C, Tonon F, Lazarevic D, et al: HMGA1 promotes breast cancer angiogenesis supporting the stability, nuclear localization and transcriptional activity of FOXM1. J Exp Clin Cancer Res. 38:3132019. View Article : Google Scholar : PubMed/NCBI
26	Wei F, Zhang T, Deng SC, Wei JC, Yang P, Wang Q, Chen ZP, Li WL, Chen HC, Hu H and Cao J: PD-L1 promotes colorectal cancer stem cell expansion by activating HMGA1-dependent signaling pathways. Cancer Lett. 450:1–13. 2019. View Article : Google Scholar : PubMed/NCBI
27	Zhong J, Liu C, Zhang QH, Chen L, Shen YY, Chen YJ, Zeng X, Zu XY and Cao RX: TGF-β1 induces HMGA1 expression: The role of HMGA1 in thyroid cancer proliferation and invasion. Int J Oncol. 50:1567–1578. 2017. View Article : Google Scholar : PubMed/NCBI