Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3

Authors: Hao Hu, Yandong Wang, Xiangya Ding, Yuan He, Zipeng Lu, Pengfei Wu, Lei Tian, Hao Yuan, Dongfang Liu, Guodong Shi, Tianfang Xia, Jie Yin, Baobao Cai, Yi Miao, Kuirong Jiang

Published in: Molecular Cancer | Issue 1/2018

Login to get access

Abstract

Background

Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can ‘act in cis’ to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear.

Methods

The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro.

Results

Here, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3.

Conclusions

Together, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.
Literature
1.
Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518:495–501.CrossRefPubMedPubMedCentral
2.
Hessmann E, Johnsen SA, Siveke JT, Ellenrieder V. Epigenetic treatment of pancreatic cancer: is there a therapeutic perspective on the horizon? Gut. 2017;66:168–79.CrossRefPubMed
3.
Zhan HX, JW X, Wu D, Zhang TP, SY H. Pancreatic cancer stem cells: new insight into a stubborn disease. Cancer Lett. 2015;357:429–37.CrossRefPubMed
4.
Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C, Sasor A, Borg D, Bauden M, Andersson R. Pancreatic cancer: yesterday, today and tomorrow. Future Oncol. 2016;12:1929–46.CrossRefPubMed
5.
6.
7.
Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013;20:300–7.CrossRefPubMed
8.
9.
Elling R, Chan J, Fitzgerald KA. Emerging role of long noncoding RNAs as regulators of innate immune cell development and inflammatory gene expression. Eur J Immunol. 2016;46:504–12.CrossRefPubMedPubMedCentral
10.
Kwok ZH, Tay Y. Long noncoding RNAs: lincs between human health and disease. Biochem Soc Trans. 2017;45:805–12.CrossRefPubMed
11.
Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661–7.CrossRefPubMed
12.
Fang Y, Wang J, Wu F, Song Y, Zhao S, Zhang Q. Long non-coding RNA HOXA-AS2 promotes proliferation and invasion of breast cancer by acting as a miR-520c-3p sponge. Oncotarget. 2017;8:46090–103.PubMedPubMedCentral
13.
CE H, PZ D, Zhang HD, Huang GJ. Long Noncoding RNA CRNDE Promotes proliferation of gastric cancer cells by targeting miR-145. Cell Physiol Biochem. 2017;42:13–21.CrossRef
14.
Rigoutsos I, Lee SK, Nam SY, Anfossi S, Pasculli B, Pichler M, Jing Y, Rodriguez-Aguayo C, Telonis AG, Rossi S, et al. N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. Genome Biol. 2017;18:98.CrossRefPubMedPubMedCentral
15.
Lu X, Zhou C, Li R, Deng Y, Zhao L, Zhai W. Long Noncoding RNA AFAP1-AS1 Promoted Tumor Growth and Invasion in Cholangiocarcinoma. Cell Physiol Biochem. 2017;42:222–30.CrossRefPubMed
16.
Wang Y, Liu Z, Yao B, Li Q, Wang L, Wang C, Dou C, Xu M, Liu Q, Tu K. Long non-coding RNA CASC2 suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells through CASC2/miR-367/FBXW7 axis. Mol Cancer. 2017;16:123.CrossRefPubMedPubMedCentral
17.
Zhan HX, Wang Y, Li C, JW X, Zhou B, Zhu JK, Han HF, Wang L, Wang YS, SY H. LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway. Cancer Lett. 2016;374:261–71.CrossRefPubMed
18.
Zheng S, Chen H, Wang Y, Gao W, Fu Z, Zhou Q, Jiang Y, Lin Q, Tan L, Ye H, et al. Long non-coding RNA LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin in a TNFRSF10A-related manner. Cancer Lett. 2016;371:354–65.CrossRefPubMed
19.
Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143:46–58.CrossRefPubMedPubMedCentral
20.
Luo S, JY L, Liu L, Yin Y, Chen C, Han X, Wu B, Xu R, Liu W, Yan P, et al. Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 2016;18:637–52.CrossRefPubMed
21.
Engreitz JM, Haines JE, Perez EM, Munson G, Chen J, Kane M, McDonel PE, Guttman M, Lander ES. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature. 2016;539:452–5.CrossRefPubMed
22.
Strobel O, Hinz U, Gluth A, Hank T, Hackert T, Bergmann F, Werner J, Buchler MW. Pancreatic adenocarcinoma: number of positive nodes allows to distinguish several N categories. Ann Surg. 2015;261:961–9.CrossRefPubMed
23.
Allen PJ, Kuk D, Castillo CF, Basturk O, Wolfgang CL, Cameron JL, Lillemoe KD, Ferrone CR, Morales-Oyarvide V, He J, et al. Multi-institutional validation study of the American joint commission on cancer (8th edition) changes for T and N staging in patients with pancreatic adenocarcinoma. Ann Surg. 2017;265:185–91.CrossRefPubMedPubMedCentral
24.
Li J, Liu D, Hua R, Zhang J, Liu W, Huo Y, Cheng Y, Hong J, Sun Y. Long non-coding RNAs expressed in pancreatic ductal adenocarcinoma and lncRNA BC008363 an independent prognostic factor in PDAC. Pancreatology. 2014;14:385–90.CrossRefPubMed
25.
Qu S, Yang X, Song W, Sun W, Li X, Wang J, Zhong Y, Shang R, Ruan B, Zhang Z, et al. Downregulation of lncRNA-ATB correlates with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 2016;37:3933–8.CrossRefPubMed
26.
Gao S, Wang P, Hua Y, Xi H, Meng Z, Liu T, Chen Z, Liu L. ROR functions as a ceRNA to regulate Nanog expression by sponging miR-145 and predicts poor prognosis in pancreatic cancer. Oncotarget. 2016;7:1608–18.PubMed
27.
Li L, Zhang GQ, Chen H, Zhao ZJ, Chen HZ, Liu H, Wang G, Jia YH, Pan SH, Kong R, et al. Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer. Oncotarget. 2016;7:71773–81.PubMedPubMedCentral
28.
Ying H, Dey P, Yao W, Kimmelman AC, Draetta GF, Maitra A, DePinho RA. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2016;30:355–85.CrossRefPubMedPubMedCentral
29.
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13:97–110.CrossRefPubMed
30.
Yang G, Liang Y, Zheng T, Song R, Wang J, Shi H, Sun B, Xie C, Li Y, Han J, et al. FCN2 inhibits epithelial-mesenchymal transition-induced metastasis of hepatocellular carcinoma via TGF-beta/Smad signaling. Cancer Lett. 2016;378:80–6.CrossRefPubMed
31.
32.
33.
Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10:210–5.CrossRefPubMed
34.
Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol. 2013;270:70–6.CrossRefPubMed
35.
Fan SH, Wang YY, Lu J, Zheng YL, DM W, Li MQ, Hu B, Zhang ZF, Cheng W, Shan Q. Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome. PLoS One. 2014;9:e89961.CrossRefPubMedPubMedCentral
36.
37.
Wang H, Wang Y, Du Q, Lu P, Fan H, Lu J, Hu R. Inflammasome-independent NLRP3 is required for epithelial-mesenchymal transition in colon cancer cells. Exp Cell Res. 2016;342:184–92.CrossRefPubMed
38.
Yang D, Cao X, Wang F, Jiang H, Feng D, Guo H, Du L, Jin Y, Chen Y, Yin X, Li C. LFG-500, a novel synthetic flavonoid, suppresses epithelial-mesenchymal transition in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment. Cancer Lett. 2017;400:137–48.CrossRefPubMed
Metadata
Title
Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3
Authors
Hao Hu
Yandong Wang
Xiangya Ding
Yuan He
Zipeng Lu
Pengfei Wu
Lei Tian
Hao Yuan
Dongfang Liu
Guodong Shi
Tianfang Xia
Jie Yin
Baobao Cai
Yi Miao
Kuirong Jiang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0761-9

Other articles of this Issue 1/2018

Molecular Cancer 1/2018 Go to the issue

Review

Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer

Research

Wnt-signaling enhances neural crest migration of melanoma cells and induces an invasive phenotype

Review

Epigenetics in ovarian cancer: premise, properties, and perspectives

Research

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation

Review

Pathological bases and clinical impact of long noncoding RNAs in prostate cancer: a new budding star

Research

Linc00210 drives Wnt/β-catenin signaling activation and liver tumor progression through CTNNBIP1-dependent manner
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits