microRNA‑23a promotes cell growth and metastasis in gastric cancer via targeting SPRY2‑mediated ERK signaling Retraction in /10.3892/ol.2021.12960

Li,Yingjia; Chen,Hui; She,Pengfei; Chen,Ti; Chen,Lihua; Yuan,Jinling; Jiang,Botao

doi:10.3892/ol.2018.8374

microRNA‑23a promotes cell growth and metastasis in gastric cancer via targeting SPRY2‑mediated ERK signaling

Retraction in: /10.3892/ol.2021.12960

Authors:
- Yingjia Li
- Hui Chen
- Pengfei She
- Ti Chen
- Lihua Chen
- Jinling Yuan
- Botao Jiang
View Affiliations

Affiliations: Clinical Laboratory, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Neurology, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China
Published online on: March 29, 2018 https://doi.org/10.3892/ol.2018.8374
Pages: 8433-8441
Copyright: © Li 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

microRNAs (miRs) serve important roles in various human cancer types. Recently, miR‑23a has been indicated as an oncogene in gastric cancer, but the underlying mechanism remains unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction and western blot analysis was used to explore the effects of miR‑23a in gastric cancer. Additionally, cell proliferation, migration and invasion were examined using an MTT assay, wound healing assay and Transwell assay, respectively. Furthermore, a luciferase reporter gene assay was used to confirm the target association. It was determined that miR‑23a was significantly upregulated in gastric cancer tissues and cell lines compared with adjacent tissues, and a normal gastric epithelial cell line. Furthermore, its upregulation was significantly associated with cancer progression and poor prognosis of patients. Knockdown of miR‑23a caused a notable reduction in the proliferation, migration and invasion of gastric cancer AGS cells. Sprouty homolog 2 (SPRY2) was then predicted to be target gene of miR‑23a. A luciferase reporter gene assay data demonstrated that miR‑23a has the ability to directly bind to the 3'‑untranslational region of SPRY2 mRNA. Further investigation demonstrated that SPRY2 was significantly downregulated in gastric cancer tissues and cell lines, and the protein expression of SPRY2 was negatively regulated by miR‑23a in AGS cells. Furthermore, knockdown of SPRY2 reduced the suppressive effects of miR‑23a inhibition in AGS cell proliferation, migration and invasion. In addition, the activity of extracellular signal‑regulated kinase (ERK) signaling was also inhibited by the miR‑23a/SPRY2 knockdown in AGS cells. The present study indicated that miR‑23a serves a promoting role in gastric cancer via targeting SPRY2 and downstream ERK signaling.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Piazuelo MB and Correa P: Gastric cancer: Overview. Colomb Med (Cali). 44:192–201. 2013.PubMed/NCBI
4	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
5	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
6	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar : PubMed/NCBI
7	Zhang X, Cai D, Meng L and Wang B: MicroRNA-124 inhibits proliferation, invasion, migration and epithelial-mesenchymal transition of cervical carcinoma cells by targeting astrocyte-elevated gene-1. Oncol Rep. 36:2321–2328. 2016. View Article : Google Scholar : PubMed/NCBI
8	Zhu K, He Y, Xia C, Yan J, Hou J, Kong D, Yang Y and Zheng G: MicroRNA-15a inhibits proliferation and induces apoptosis in CNE1 nasopharyngeal carcinoma cells. Oncol Res. 24:145–151. 2016. View Article : Google Scholar : PubMed/NCBI
9	Wang G, Fu Y, Liu G, Ye Y and Zhang X: miR-218 inhibits proliferation, migration, and EMT of gastric cancer cells by targeting WASF3. Oncol Res. 25:355–364. 2017. View Article : Google Scholar : PubMed/NCBI
10	Lv H, Zhang Z, Wang Y, Li C, Gong W and Wang X: MicroRNA-92a promotes colorectal cancer cell growth and migration by inhibiting KLF4. Oncol Res. 23:283–290. 2016. View Article : Google Scholar
11	Liu X, Li J, Yu Z, Sun R and Kan Q: MiR-935 promotes liver cancer cell proliferation and migration by targeting SOX7. Oncol Res. 25:427–435. 2017. View Article : Google Scholar : PubMed/NCBI
12	Li X, Li Y and Lu H: MiR-1193 suppresses proliferation and invasion of human breast cancer cells through directly targeting IGF2BP2. Oncol Res. 25:579–585. 2017. View Article : Google Scholar : PubMed/NCBI
13	Liu P, Wang C, Ma C, Wu Q, Zhang W and Lao G: MicroRNA-23a regulates epithelial-to-mesenchymal transition in endometrial endometrioid adenocarcinoma by targeting SMAD3. Cancer Cell Int. 16:672016. View Article : Google Scholar : PubMed/NCBI
14	He Y, Meng C, Shao Z, Wang H and Yang S: MiR-23a functions as a tumor suppressor in osteosarcoma. Cell Physiol Biochem. 34:1485–1496. 2014. View Article : Google Scholar : PubMed/NCBI
15	Zhu LH, Liu T, Tang H, Tian RQ, Su C, Liu M and Li X: MicroRNA-23a promotes the growth of gastric adenocarcinoma cell line MGC803 and downregulates interleukin-6 receptor. FEBS J. 277:3726–3734. 2010. View Article : Google Scholar : PubMed/NCBI
16	Liu X, Liu Q, Fan Y, Wang S, Liu X, Zhu L, Liu M and Tang H: Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells. FEBS Lett. 588:3160–3169. 2014. View Article : Google Scholar : PubMed/NCBI
17	Lim J, Wong ES, Ong SH, Yusoff P, Low BC and Guy GR: Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. J Biol Chem. 275:32837–32845. 2000. View Article : Google Scholar : PubMed/NCBI
18	Lim J, Yusoff P, Wong ES, Chandramouli S, Lao DH, Fong CW and Guy GR: The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes. Mol Cell Biol. 22:7953–7966. 2002. View Article : Google Scholar : PubMed/NCBI
19	Liu C, Liang S, Xiao S, Lin Q, Chen X, Wu Y and Fu J: MicroRNA-27b inhibits Spry2 expression and promotes cell invasion in glioma U251 cells. Oncol Lett. 9:1393–1397. 2015. View Article : Google Scholar : PubMed/NCBI
20	Chandramouli S, Yu CY, Yusoff P, Lao DH, Leong HF, Mizuno K and Guy GR: Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling. J Biol Chem. 283:1679–1691. 2008. View Article : Google Scholar : PubMed/NCBI
21	Wu G, Qin XQ, Guo JJ, Li TY and Chen JH: AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel. Int J Clin Exp Pathol. 7:1449–1458. 2014.PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Dalta Dalta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Yim DG, Ghosh S, Guy GR and Virshup DM: Casein kinase 1 regulates Sprouty2 in FGF-ERK signaling. Oncogene. 34:474–484. 2015. View Article : Google Scholar : PubMed/NCBI
24	Deng J, Lei W, Xiang X, Zhang L, Yu F, Chen J, Feng M and Xiong J: MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly targeting Yap1. Tumour Biol. 36:6823–6831. 2015. View Article : Google Scholar : PubMed/NCBI
25	Lu WD, Zuo Y, Xu Z and Zhang M: MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer. World J Gastroenterol. 21:4564–4573. 2015. View Article : Google Scholar : PubMed/NCBI
26	Li QL, Yang Y, Zhang L, Chen H, Pan D and Xie WJ: MicroRNA-181b inhibits glycolysis in gastric cancer cells via targeting hexokinase 2 gene. Cancer Biomark. 17:75–81. 2016. View Article : Google Scholar : PubMed/NCBI
27	Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, Sun L, Ji G, Shi Y, Han Z, et al: miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 9:824–833. 2011. View Article : Google Scholar : PubMed/NCBI
28	An J, Pan Y, Yan Z, Li W, Cui J, Yuan J, Tian L, Xing R and Lu Y: MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells. J Cell Biochem. 114:2160–2169. 2013. View Article : Google Scholar : PubMed/NCBI
29	Ma G, Dai W, Sang A, Yang X and Gao C: Upregulation of microRNA-23a/b promotes tumor progression and confers poor prognosis in patients with gastric cancer. Int J Clin Exp Pathol. 7:8833–8840. 2014.PubMed/NCBI
30	Zhu L, Tian J, Chen L, Wang M, Xiong Y, Zhang G, Li S and Yuan L: Effect of blocking endogenous miR-23a on the proliferation and invasion in gastric adenocarcinoma cell line MGC803. Nan Fang Yi Ke Da Xue Xue Bao. 33:678–683. 2013.(In Chinese). PubMed/NCBI
31	Mei Y, Bian C, Li J, Du Z, Zhou H, Yang Z and Zhao RC: miR-21 modulates the ERK-MAPK signaling pathway by regulating SPRY2 expression during human mesenchymal stem cell differentiation. J Cell Biochem. 114:1374–1384. 2013. View Article : Google Scholar : PubMed/NCBI
32	Jiang J, Yi B, Qin C, Ding S and Cao W: Upregulation of microRNA27b contributes to the migration and invasion of gastric cancer cells via the inhibition of sprouty2-mediated ERK signaling. Mol Med Rep. 13:2267–2272. 2016. View Article : Google Scholar : PubMed/NCBI