LncRNA MALAT1/miR-30a/SOX4 pathway regulates proliferation, invasion and migration of bladder cancer cells

doi:10.13418/j.issn.1001-165x.2020.03.011

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (3) : 295-300. DOI: 10.13418/j.issn.1001-165x.2020.03.011

LUO Qian, LV Jie, WANG Ning

Author information +

History +

Abstract

Objective　To elucidate the molecular mechanism and potential therapeutic targets of bladder cancer and explore the regulatory mechanism of MALAT1-miR-30a-5p-SOX4 axis in bladder cancer. Methods　Quantitative real-time PCR (RT-PCR) was used to detect the expressions of mir-30a-5p, MALAT1 and SOX4 in bladder cancer cells. Luciferase reporter assay was used to verify the biological relationship between mir-30a-5p and SOX4.The biological functions of mir-30a-5p and SOX4 in T24 cells were studied by in vitro experiments, including the detection of cell proliferation by CCK-8 method, cell invasion by Transwell and cell migration by wound healing method. Western blot was used to detect protein expression. Results 　In bladder cancer cells, MALAT1 expression was up-regulated and mir-30a-5p expression was down-regulated (P<0.01). Sh-MALAT1 inhibited the proliferation, invasion and migration of T24 cells. Further studies showed that MALAT1 can directly interact with mir-30a-5p, and SOX4 is the target of miR-30a-5p, and SOX4 can be down-regulated by over-expression mir-30a-5p.　Conclusions　MALAT1 knockout can relieve the inhibition of mir-30a-5p by MALAT1 and thus inhibiting SOX4. MALAT1 may regulate the proliferation, invasion and metastasis of bladder cancer by regulating the mir-30a/SOX4 pathway.

Key words

Bladder cancer / 　MALAT1 / 　miR-30a / 　SOX4

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LUO Qian, LV Jie, WANG Ning. LncRNA MALAT1/miR-30a/SOX4 pathway regulates proliferation, invasion and migration of bladder cancer cells[J]. Chinese Journal of Clinical Anatomy. 2020, 38(3): 295-300 https://doi.org/10.13418/j.issn.1001-165x.2020.03.011

References

[1] Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends[J]. Eur Urol, 2017, 71(1): 96-108.
[2] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5): E359-E386.
[3] Gao D, Lv AE, Li HP, et al. LncRNA MALAT-1 elevates HMGB1 to promote autophagy resulting in inhibition of tumor cell apoptosis in multiple myeloma[J]. J Cell Biochem, 2017, 118(10): 3341-3348.
[4] Ren S, Liu Y, Xu W, et al. Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer[J]. J Urol, 2013, 190(6): 2278-2287.
[5] Zhang R, Xia Y, Wang Z, et al. Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer[J]. Biochem Biophys Res Commun, 2017, 490(2): 406-414.
[6] Hu ZY, Wang XY, Guo WB, et al. Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells[J]. Oncotarget, 2016, 7(10): 11733-11743.
[7] Wu J, Weng Y, He F, et al. LncRNA MALAT-1 competitively regulates miR-124 to promote EMT and development of non-small-cell lung cancer[J]. Anticancer Drugs, 2018, 29(7): 628-636.
[8] Zhang X, He X, Liu Y, et al. MiR-101-3p inhibits the growth and metastasis of non-small cell lung cancer through blocking PI3K/AKT signal pathway by targeting MALAT-1[J]. Biomedecine Pharmacother, 2017, 93: 1065-1073.
[9] Zhuo M, Yuan C, Han T, et al. A novel feedback loop between high MALAT-1 and low miR-200c-3p promotes cell migration and invasion in pancreatic ductal adenocarcinoma and is predictive of poor prognosis[J]. BMC Cancer, 2018, 18(1): 1032.
[10]Ying L, Chen Q, Wang Y, et al. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition[J]. Mol Biosyst, 2012, 8(9): 2289-2294.
[11] Tang D, Yang Z, Long F, et al. Inhibition of MALAT1 reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer[J]. Cell Signal, 2019, 57: 21-28.
[12]Baraniskin A, Birkenkamp-demtroder K, Maghnouj A, et al. MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL[J]. Carcinogenesis, 2012, 33(4): 732-739.
[13]Chung YH, Li SC, Kao YH, et al. MiR-30a-5p inhibits epithelial-to-mesenchymal transition and upregulates expression of tight junction protein claudin-5 in human upper tract urothelial carcinoma cells[J]. Int J Mol Sci, 2017, 18(8): E1826.
[14]Jiang X, Du L, Wang L, et al. Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer[J]. Int J Cancer, 2015, 136(4): 854-862.
[15]Pan Y, Tong S, Cui R, et al. Long non-coding MALAT1 functions as a competing endogenous RNA to regulate vimentin expression by sponging miR-30a-5p in hepatocellular carcinoma[J]. Cell Physiol Biochem, 2018, 50(1): 108-120.
[16]Shen H, Blijlevens M, Yang N, et al. Sox4 expression confers bladder cancer stem cell properties and predicts for poor patient outcome[J]. Int J Biol Sci, 2015, 11(12): 1363-1375.
[17]Gunes S, Yegin Z, Sullu Y, et al. SOX4 expression levels in urothelial bladder carcinoma[J]. Pathol Res Pract, 2011, 207(7): 423-427.
[18]Aaboe M, Birkenkamp-Demtroder K, Wiuf C, et al. SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization[J]. Cancer Res, 2006, 66(7): 3434-3442.