Long Non-coding RNA Small Nucleolar RNA Host Gene 6 Aggravates Pancreatic Cancer Through Upregulation of Far Upstream Element Binding Protein 1 by Sponging MicroRNA-26a-5p

Overview

Journal Chin Med J (Engl)

Specialty General Medicine

Date 2020 May 21

PMID 32433053

Citations 4

Authors

Xing-Xing Zhang

Hua Chen

Hui-Ying Li

Rui Chen

Lei He

Juan-Li Yang

Lin-Lin Xiao

Jin-Lian Chen

Affiliations

Soon will be listed here.

Abstract

Background: Pancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).

Methods: SNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.

Results: Compared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t = 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t = 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t = 7.70, P = 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t = 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t = 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs. 0.32 ± 0.03, t = 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t = 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.

Conclusion: Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.

Citing Articles

Circulating autoantibodies to alpha-enolase (ENO1) and far upstream element-binding protein 1 (FUBP1) are negative prognostic factors for pancreatic cancer patient survival.

Curcio C, Rosso T, Brugiapaglia S, Guadagnin G, Giordano D, Castellino B Clin Exp Med. 2023; 23(8):5089-5100.

PMID: 37910256 PMC: 10725354. DOI: 10.1007/s10238-023-01236-5.

The Role of lncRNA-miR-26a-mRNA Network in Cancer Progression and Treatment.

Zhu J, Wang L Biochem Genet. 2023; 62(3):1443-1461.

PMID: 37730965 DOI: 10.1007/s10528-023-10475-w.

Microbiome and MicroRNA or Long Non-Coding RNA-Two Modern Approaches to Understanding Pancreatic Ductal Adenocarcinoma.

Izdebska W, Daniluk J, Niklinski J J Clin Med. 2023; 12(17).

PMID: 37685710 PMC: 10488817. DOI: 10.3390/jcm12175643.

Differentially Expressed Long Noncoding RNAs Involved in FUBP1 Promoting Hepatocellular Carcinoma Cells Proliferation.

Li X, Yu H, Xu F, Wu Y, Sheng J Biomed Res Int. 2021; 2021:6664519.

PMID: 33954195 PMC: 8063849. DOI: 10.1155/2021/6664519.

References

Kamisawa T, Wood L, Itoi T, Takaori K . Pancreatic cancer. Lancet. 2016; 388(10039):73-85. DOI: 10.1016/S0140-6736(16)00141-0. View

Gao J, Zeng K, Liu Y, Gao L, Liu L . LncRNA SNHG5 promotes growth and invasion in melanoma by regulating the miR-26a-5p/TRPC3 pathway. Onco Targets Ther. 2019; 12:169-179. PMC: 6309782. DOI: 10.2147/OTT.S184078. View

Deng J, He M, Chen L, Chen C, Zheng J, Cai Z . The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in pancreatic cancer cell proliferation and decreased patient survival. PLoS One. 2013; 8(10):e76450. PMC: 3792981. DOI: 10.1371/journal.pone.0076450. View

Batchu R, Gruzdyn O, Qazi A, Kaur J, Mahmud E, Weaver D . Enhanced phosphorylation of p53 by microRNA-26a leading to growth inhibition of pancreatic cancer. Surgery. 2015; 158(4):981-6. DOI: 10.1016/j.surg.2015.05.019. View

Zhang X, Liu Z, Shu Q, Yuan S, Xing Z, Song J . LncRNA SNHG6 functions as a ceRNA to regulate neuronal cell apoptosis by modulating miR-181c-5p/BIM signalling in ischaemic stroke. J Cell Mol Med. 2019; 23(9):6120-6130. PMC: 6714173. DOI: 10.1111/jcmm.14480. View

Zhao D, Zhang Y, Song L . MiR-16-1 Targeted Silences Far Upstream Element Binding Protein 1 to Advance the Chemosensitivity to Adriamycin in Gastric Cancer. Pathol Oncol Res. 2017; 24(3):483-488. DOI: 10.1007/s12253-017-0263-x. View

Duan J, Bao X, Ma X, Zhang Y, Ni D, Wang H . Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma. PLoS One. 2017; 12(1):e0169852. PMC: 5226774. DOI: 10.1371/journal.pone.0169852. View

Assmann T, Milagro F, Martinez J . Crosstalk between microRNAs, the putative target genes and the lncRNA network in metabolic diseases. Mol Med Rep. 2019; 20(4):3543-3554. PMC: 6755190. DOI: 10.3892/mmr.2019.10595. View

Sun Y, Wei G, Luo H, Wu W, Skogerbo G, Luo J . The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes. Oncogene. 2017; 36(49):6774-6783. DOI: 10.1038/onc.2017.286. View

10.

Fan P, Ma J, Jin X . Far upstream element-binding protein 1 is up-regulated in pancreatic cancer and modulates immune response by increasing programmed death ligand 1. Biochem Biophys Res Commun. 2018; 505(3):830-836. DOI: 10.1016/j.bbrc.2018.10.009. View

11.

Yuan Y, Zhou J, Zhang Y, Xu M, Wu J, Li W . Identification of key genes and pathways downstream of the β-catenin-TCF7L1 complex in pancreatic cancer cells using bioinformatics analysis. Oncol Lett. 2019; 18(2):1117-1132. PMC: 6607041. DOI: 10.3892/ol.2019.10444. View

12.

Zhu X, Yang G, Xu J, Zhang C . Silencing of SNHG6 induced cell autophagy by targeting miR-26a-5p/ULK1 signaling pathway in human osteosarcoma. Cancer Cell Int. 2019; 19:82. PMC: 6448242. DOI: 10.1186/s12935-019-0794-1. View

13.

Hoang V, Verma D, Godavarthy P, Llavona P, Steiner M, Gerlach K . The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia. Leukemia. 2019; 33(7):1700-1712. DOI: 10.1038/s41375-018-0358-8. View

14.

Huang Z, Ge H, Yang C, Cai Y, Chen Z, Tian W . MicroRNA-26a-5p inhibits breast cancer cell growth by suppressing RNF6 expression. Kaohsiung J Med Sci. 2019; 35(8):467-473. DOI: 10.1002/kjm2.12085. View

15.

Costello E, Neoptolemos J . Pancreatic cancer in 2010: new insights for early intervention and detection. Nat Rev Gastroenterol Hepatol. 2011; 8(2):71-3. DOI: 10.1038/nrgastro.2010.214. View

16.

Li F, Li Q, Wu X . Construction and analysis for differentially expressed long non-coding RNAs and MicroRNAs mediated competing endogenous RNA network in colon cancer. PLoS One. 2018; 13(2):e0192494. PMC: 5805314. DOI: 10.1371/journal.pone.0192494. View

17.

Li K, Ma Y, Tian Y, Xu X, Gao Y, He Y . Silencing lncRNA SNHG6 suppresses proliferation and invasion of breast cancer cells through miR-26a/VASP axis. Pathol Res Pract. 2019; 215(10):152575. DOI: 10.1016/j.prp.2019.152575. View

18.

Liang R, Xiao G, Wang M, Li X, Li Y, Hui Z . SNHG6 functions as a competing endogenous RNA to regulate E2F7 expression by sponging miR-26a-5p in lung adenocarcinoma. Biomed Pharmacother. 2018; 107:1434-1446. DOI: 10.1016/j.biopha.2018.08.099. View

19.

Debaize L, Troadec M . The master regulator FUBP1: its emerging role in normal cell function and malignant development. Cell Mol Life Sci. 2018; 76(2):259-281. PMC: 11105487. DOI: 10.1007/s00018-018-2933-6. View

20.

Yang Y, Sun Y, Wang H, Li H, Zhang M, Zhou L . MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer. Oncol Lett. 2018; 16(6):7295-7301. PMC: 6256293. DOI: 10.3892/ol.2018.9513. View