Skip to main content
Erschienen in: Gastric Cancer 2/2020

26.08.2019 | Original Article

LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway

verfasst von: Wei Zong, Wei Feng, Yun Jiang, Yaning Cao, Yuchen Ke, Xin Shi, Shaoqing Ju, Hui Cong, Xudong Wang, Ming Cui, Rongrong Jing

Erschienen in: Gastric Cancer | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Long non-coding RNAs (lncRNAs) have emerged as important roles in gastric cancer (GC). However, the role of the dysregulated lncRNAs in GC remained large unknown. We investigated the clinical significance, biological function and mechanism of CTC-497E21.4 in GC.

Methods

Firstly, RTFQ-PCR was used to detect the expression of CTC-497E21.4 in GC. Furthermore, knockdown of CTC-497E21.4 was conducted to assess the effect of CTC-497E21.4 in vitro and vivo. Subcellular localization of CTC-497E21.4 was determined by nuclear plasmolysis PCR and FISH. We also predicted CTC-497E21.4 binding miRNAs and downstream target genes and evaluated its regulation of miR-22 by acting as a ceRNA.

Result

CTC-497E21.4 was upregulated in GC tissues and GC cell lines (P < 0.05), and the expression was associated with depth of invasion, lymph node metastasis, and neurological invasion. Besides, knockdown of CTC-497E21.4 inhibited cell proliferation, invasion and promoted cell cycle arrest in vitro and inhibited tumorigenesis in vivo. Mechanistic investigations indicated that CTC-497E21.4 acted as a ceRNA for miR-22 and regulated NET1 expression. CTC-497E21.4/miR-22-3p/NET1 participated in the RhoA signaling pathway in the GC progression.

Conclusion

CTC-497E21.4 competed with miR-22 to regulate the expression of NET1 and regulated the malignant progression of GC through RhoA signaling pathway.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRef Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRef
2.
Zurück zum Zitat Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef
3.
Zurück zum Zitat Chen W, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef Chen W, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef
4.
Zurück zum Zitat Zong L, et al. The challenge of screening for early gastric cancer in China. Lancet. 2016;388(10060):2606.CrossRef Zong L, et al. The challenge of screening for early gastric cancer in China. Lancet. 2016;388(10060):2606.CrossRef
5.
Zurück zum Zitat Van Cutsem E, et al. Gastric cancer. Lancet. 2016;388(10060):2654–64.CrossRef Van Cutsem E, et al. Gastric cancer. Lancet. 2016;388(10060):2654–64.CrossRef
6.
Zurück zum Zitat Salmena L, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8.CrossRef Salmena L, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8.CrossRef
7.
Zurück zum Zitat Sun M, et al. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1. Cancer Res. 2016;76(21):6299–310.CrossRef Sun M, et al. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1. Cancer Res. 2016;76(21):6299–310.CrossRef
8.
Zurück zum Zitat Zong W, et al. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer. Clin Chem Lab Med. 2018;56(11):1828–37.CrossRef Zong W, et al. Long non-coding RNA-mediated regulation of signaling pathways in gastric cancer. Clin Chem Lab Med. 2018;56(11):1828–37.CrossRef
9.
Zurück zum Zitat Guo LL, et al. Competing endogenous RNA networks and gastric cancer. World J Gastroenterol. 2015;21(41):11680–7.CrossRef Guo LL, et al. Competing endogenous RNA networks and gastric cancer. World J Gastroenterol. 2015;21(41):11680–7.CrossRef
10.
Zurück zum Zitat Chen B, et al. Long non-coding RNA NNT-AS1 sponges miR-424/E2F1 to promote the tumorigenesis and cell cycle progression of gastric cancer. J Cell Mol Med. 2018;22(10):4751–9.CrossRef Chen B, et al. Long non-coding RNA NNT-AS1 sponges miR-424/E2F1 to promote the tumorigenesis and cell cycle progression of gastric cancer. J Cell Mol Med. 2018;22(10):4751–9.CrossRef
11.
Zurück zum Zitat Xu M, et al. The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer. 2018;17(1):141.CrossRef Xu M, et al. The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer. 2018;17(1):141.CrossRef
12.
Zurück zum Zitat Gu J, et al. Identification of aberrantly expressed long non-coding RNAs in stomach adenocarcinoma. Oncotarget. 2017;8(30):49201–16.CrossRef Gu J, et al. Identification of aberrantly expressed long non-coding RNAs in stomach adenocarcinoma. Oncotarget. 2017;8(30):49201–16.CrossRef
13.
Zurück zum Zitat Zong W, et al. Evaluating the diagnostic and prognostic value of serum long non-coding RNA CTC-497E21.4 in gastric cancer. Clin Chem Lab Med. 2019;57(7):1063–72.CrossRef Zong W, et al. Evaluating the diagnostic and prognostic value of serum long non-coding RNA CTC-497E21.4 in gastric cancer. Clin Chem Lab Med. 2019;57(7):1063–72.CrossRef
14.
Zurück zum Zitat Seitz AK, et al. Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer. Sci Rep. 2017;7(1):395.CrossRef Seitz AK, et al. Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer. Sci Rep. 2017;7(1):395.CrossRef
15.
Zurück zum Zitat He W, et al. Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. J Clin Invest. 2018;128(2):861–75.CrossRef He W, et al. Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. J Clin Invest. 2018;128(2):861–75.CrossRef
16.
Zurück zum Zitat Zhang X, et al. miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting Sirt1. Biol Res. 2017;50(1):27.CrossRef Zhang X, et al. miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting Sirt1. Biol Res. 2017;50(1):27.CrossRef
17.
Zurück zum Zitat Zhang H, et al. MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Lett. 2015;356(2 Pt B):781–90.CrossRef Zhang H, et al. MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Lett. 2015;356(2 Pt B):781–90.CrossRef
18.
Zurück zum Zitat Wang X, et al. MiR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151. Biochem Biophys Res Commun. 2014;445(1):175–9.CrossRef Wang X, et al. MiR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151. Biochem Biophys Res Commun. 2014;445(1):175–9.CrossRef
19.
Zurück zum Zitat Zuo QF, et al. MicroRNA-22 inhibits tumor growth and metastasis in gastric cancer by directly targeting MMP14 and Snail. Cell Death Dis. 2015;6:e2000.CrossRef Zuo QF, et al. MicroRNA-22 inhibits tumor growth and metastasis in gastric cancer by directly targeting MMP14 and Snail. Cell Death Dis. 2015;6:e2000.CrossRef
20.
Zurück zum Zitat Carr HS, et al. Regulation of focal adhesion kinase activation, breast cancer cell motility, and amoeboid invasion by the RhoA guanine nucleotide exchange factor Net1. Mol Cell Biol. 2013;33(14):2773–866.CrossRef Carr HS, et al. Regulation of focal adhesion kinase activation, breast cancer cell motility, and amoeboid invasion by the RhoA guanine nucleotide exchange factor Net1. Mol Cell Biol. 2013;33(14):2773–866.CrossRef
21.
Zurück zum Zitat Chen C, Ji Q. Net1, a therapeutic potential target for cancer. Hum Pathol. 2018;71:168.CrossRef Chen C, Ji Q. Net1, a therapeutic potential target for cancer. Hum Pathol. 2018;71:168.CrossRef
22.
Zurück zum Zitat Zhang Y, et al. Short interfering RNA targeting Net1 reduces the angiogenesis and tumor growth of in vivo cervical squamous cell carcinoma through VEGF down-regulation. J Cell Sci. 2017;65:113–22. Zhang Y, et al. Short interfering RNA targeting Net1 reduces the angiogenesis and tumor growth of in vivo cervical squamous cell carcinoma through VEGF down-regulation. J Cell Sci. 2017;65:113–22.
23.
Zurück zum Zitat Murray D, et al. NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer. 2008;99(8):1322–9.CrossRef Murray D, et al. NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer. 2008;99(8):1322–9.CrossRef
24.
Zurück zum Zitat Zuo Y, et al. Contributions of the RhoA guanine nucleotide exchange factor Net1 to polyoma middle T antigen-mediated mammary gland tumorigenesis and metastasis. Breast Cancer Res. 2018;20(1):41.CrossRef Zuo Y, et al. Contributions of the RhoA guanine nucleotide exchange factor Net1 to polyoma middle T antigen-mediated mammary gland tumorigenesis and metastasis. Breast Cancer Res. 2018;20(1):41.CrossRef
25.
Zurück zum Zitat Chen X, et al. Long noncoding RNA LINC01234 functions as a competing endogenous RNA to regulate CBFB expression by sponging miR-204-5p in gastric cancer. Clin Cancer Res. 2018;24(8):2002–144.CrossRef Chen X, et al. Long noncoding RNA LINC01234 functions as a competing endogenous RNA to regulate CBFB expression by sponging miR-204-5p in gastric cancer. Clin Cancer Res. 2018;24(8):2002–144.CrossRef
26.
Zurück zum Zitat Lu G, et al. Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis. J Exp Clin Cancer Res. 2018;37(1):289.CrossRef Lu G, et al. Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis. J Exp Clin Cancer Res. 2018;37(1):289.CrossRef
27.
Zurück zum Zitat Hu Y, et al. Roles of competing endogenous RNAs in gastric cancer. Brief Funct Genomics. 2016;15(3):266–73.CrossRef Hu Y, et al. Roles of competing endogenous RNAs in gastric cancer. Brief Funct Genomics. 2016;15(3):266–73.CrossRef
28.
Zurück zum Zitat Zhang Y, et al. Identification of an lncRNAmiRNAmRNA interaction mechanism in breast cancer based on bioinformatic analysis. Mol Med Rep. 2017;16(4):5113–200.CrossRef Zhang Y, et al. Identification of an lncRNAmiRNAmRNA interaction mechanism in breast cancer based on bioinformatic analysis. Mol Med Rep. 2017;16(4):5113–200.CrossRef
29.
Zurück zum Zitat Zhang G, et al. LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer. Mol Cancer. 2018;17(1):87.CrossRef Zhang G, et al. LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer. Mol Cancer. 2018;17(1):87.CrossRef
30.
Zurück zum Zitat Zhang X, et al. Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res. 2018;37(1):134.CrossRef Zhang X, et al. Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res. 2018;37(1):134.CrossRef
31.
Zurück zum Zitat Cao Z, et al. The lncLocator: a subcellular localization predictor for long non-coding RNAs based on a stacked ensemble classifier. Bioinformatics. 2018;34(13):2185–94.CrossRef Cao Z, et al. The lncLocator: a subcellular localization predictor for long non-coding RNAs based on a stacked ensemble classifier. Bioinformatics. 2018;34(13):2185–94.CrossRef
32.
Zurück zum Zitat Bai Y, et al. Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression. J Cell Physiol. 2019;234(10):18837–18848.PubMedPubMedCentral Bai Y, et al. Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression. J Cell Physiol. 2019;234(10):18837–18848.PubMedPubMedCentral
33.
Zurück zum Zitat Dubash AD, et al. The small GTPase RhoA localizes to the nucleus and is activated by Net1 and DNA damage signals. PLoS ONE. 2011;6(2):e17380.CrossRef Dubash AD, et al. The small GTPase RhoA localizes to the nucleus and is activated by Net1 and DNA damage signals. PLoS ONE. 2011;6(2):e17380.CrossRef
34.
Zurück zum Zitat Carr HS, et al. Interaction of the RhoA exchange factor Net1 with discs large homolog 1 protects it from proteasome-mediated degradation and potentiates Net1 activity. J Biol Chem. 2009;284(36):24269–80.CrossRef Carr HS, et al. Interaction of the RhoA exchange factor Net1 with discs large homolog 1 protects it from proteasome-mediated degradation and potentiates Net1 activity. J Biol Chem. 2009;284(36):24269–80.CrossRef
35.
Zurück zum Zitat Ahmad HM, et al. miR-22 regulates expression of oncogenic neuro-epithelial transforming gene 1, NET1. Febs J. 2014;281(17):3904–19.CrossRef Ahmad HM, et al. miR-22 regulates expression of oncogenic neuro-epithelial transforming gene 1, NET1. Febs J. 2014;281(17):3904–19.CrossRef
36.
Zurück zum Zitat Wang W, et al. Anti-proliferative effect of auriculataoside A on B16 melanoma 4A5 cells by suppression of Cdc42-Rac1-RhoA signaling protein levels. J Nat Med. 2019;73(3):450–5.CrossRef Wang W, et al. Anti-proliferative effect of auriculataoside A on B16 melanoma 4A5 cells by suppression of Cdc42-Rac1-RhoA signaling protein levels. J Nat Med. 2019;73(3):450–5.CrossRef
37.
Zurück zum Zitat Aspenstrom P. Activated Rho GTPases in cancer-the beginning of a new paradigm. Int J Mol Sci. 2018;19(12):3949.CrossRef Aspenstrom P. Activated Rho GTPases in cancer-the beginning of a new paradigm. Int J Mol Sci. 2018;19(12):3949.CrossRef
Metadaten
Titel
LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway
verfasst von
Wei Zong
Wei Feng
Yun Jiang
Yaning Cao
Yuchen Ke
Xin Shi
Shaoqing Ju
Hui Cong
Xudong Wang
Ming Cui
Rongrong Jing
Publikationsdatum
26.08.2019
Verlag
Springer Singapore
Erschienen in
Gastric Cancer / Ausgabe 2/2020
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-019-00998-w

Weitere Artikel der Ausgabe 2/2020

Gastric Cancer 2/2020 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.