MicroRNA-448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway Retraction in /10.3892/or.2022.8424

Yu,Dan-Li; Zhang,Tao; Wu,Kun; Li,Yan; Wang,Juan; Chen,Jun; Li,Xiao-Quan; Peng,Xing-Guo; Wang,Jia-Ning; Tan,Li-Guo

doi:10.3892/or.2017.5781

MicroRNA-448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway

Retraction in: /10.3892/or.2022.8424

Authors:
- Dan-Li Yu
- Tao Zhang
- Kun Wu
- Yan Li
- Juan Wang
- Jun Chen
- Xiao-Quan Li
- Xing-Guo Peng
- Jia-Ning Wang
- Li-Guo Tan
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Affiliations: Department of Emergency, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, The 2nd Department of Internal Medicine, Dongfeng Huaguo Hospital of Shiyan City, Shiyan, Hubei 442049, P.R. China
Published online on: July 3, 2017 https://doi.org/10.3892/or.2017.5781
Pages: 1075-1082

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients. Overexpression of miR-448 suppressed PDAC cell migration and invasion, while its loss showed the opposite effects on these cellular processes. In vivo experiments revealed that miR-488 restoration prohibited liver metastasis of PDAC in nude mice. Moreover, we found that Janus kinase 1 (JAK1) was a direct target gene of miR-448 in PDAC cells. We further demonstrated that the expression of JAK1 mRNA was upregulated in PDAC tissues. Notably, the expression of JAK1 mRNA was inversely correlated with the level of miR-448 in PDAC tissues. In addition, JAK1 knockdown showed similar effects of miR-448 on the metastasis of PDAC cells. JAK1/STAT3 pathway may be involved in the function of miR-448 in PDAC cells. Taken together, these findings suggest that miR-448 functions as a tumor suppressor in the development of PDAC through targeting the JAK1/STAT3 pathway.

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1	Gomez-Rubio P, Zock JP, Rava M, Marquez M, Sharp L, Hidalgo M, Carrato A, Ilzarbe L, Michalski C, Molero X, et al: PanGenEU Study Investigators: Reduced risk of pancreatic cancer associated with asthma and nasal allergies. Gut. 66:314–322. 2017. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Zhang JJ, Zhu Y, Xie KL, Peng YP, Tao JQ, Tang J, Li Z, Xu ZK, Dai CC, Qian ZY, et al: Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. Mol Cancer. 13:1302014. View Article : Google Scholar : PubMed/NCBI
4	Palagani V, Bozko P, El Khatib M, Belahmer H, Giese N, Sipos B, Malek NP and Plentz RR: Combined inhibition of Notch and JAK/STAT is superior to monotherapies and impairs pancreatic cancer progression. Carcinogenesis. 35:859–866. 2014. View Article : Google Scholar : PubMed/NCBI
5	Tactacan CM, Phua YW, Liu L, Zhang L, Humphrey ES, Cowley M, Pinese M, Biankin AV and Daly RJ: The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling. Mol Cancer. 14:1392015. View Article : Google Scholar : PubMed/NCBI
6	Gruber R, Panayiotou R, Nye E, Spencer-Dene B, Stamp G and Behrens A: YAP1 and TAZ control pancreatic cancer initiation in mice by direct up-regulation of JAK-STAT3 signaling. Gastroenterology. 151:526–539. 2016. View Article : Google Scholar : PubMed/NCBI
7	Kang M, Ren MP, Zhao L, Li CP and Deng MM: miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1. Am J Transl Res. 7:2212–2222. 2015.PubMed/NCBI
8	Song X, Wang Z, Jin Y, Wang Y and Duan W: Loss of miR-532-5p in vitro promotes cell proliferation and metastasis by influencing CXCL2 expression in HCC. Am J Transl Res. 7:2254–2261. 2015.PubMed/NCBI
9	Huang K, Dong X, Sui C, Hu D, Xiong T, Liao S and Zhang H: MiR-223 suppresses endometrial carcinoma cells proliferation by targeting IGF-1R. Am J Transl Res. 6:841–849. 2014.PubMed/NCBI
10	Wu D, Chen B, Cui F, He X, Wang W and Wang M: Hypoxia-induced microRNA-301b regulates apoptosis by targeting Bim in lung cancer. Cell Prolif. 49:476–483. 2016. View Article : Google Scholar : PubMed/NCBI
11	Sun Y, Zhao J, Yin X, Yuan X, Guo J and Bi J: miR-297 acts as an oncogene by targeting GPC5 in lung adenocarcinoma. Cell Prolif. 49:636–643. 2016. View Article : Google Scholar : PubMed/NCBI
12	Hu S, Zhang M, Sun F, Ren L, He X, Hua J and Peng S: miR-375 controls porcine pancreatic stem cell fate by targeting 3-phosphoinositide-dependent protein kinase-1 (Pdk1). Cell Prolif. 49:395–406. 2016. View Article : Google Scholar : PubMed/NCBI
13	Ahmad A, Sethi S, Chen W, Ali-Fehmi R, Mittal S and Sarkar FH: Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis. Am J Transl Res. 6:384–390. 2014.PubMed/NCBI
14	Li P, Xue WJ, Feng Y and Mao QS: MicroRNA-205 functions as a tumor suppressor in colorectal cancer by targeting cAMP responsive element binding protein 1 (CREB1). Am J Transl Res. 7:2053–2059. 2015.PubMed/NCBI
15	Gao Y, Xue Q, Wang D, Du M, Zhang Y and Gao S: miR-873 induces lung adenocarcinoma cell proliferation and migration by targeting SRCIN1. Am J Transl Res. 7:2519–2526. 2015.PubMed/NCBI
16	Shan TD, Ouyang H, Yu T, Li JY, Huang CZ, Yang HS, Zhong W, Xia ZS and Chen QK: miRNA-30e regulates abnormal differentiation of small intestinal epithelial cells in diabetic mice by downregulating Dll4 expression. Cell Prolif. 49:102–114. 2016. View Article : Google Scholar : PubMed/NCBI
17	Huang X, Huang M, Kong L and Li Y: miR-372 suppresses tumour proliferation and invasion by targeting IGF2BP1 in renal cell carcinoma. Cell Prolif. 48:593–599. 2015. View Article : Google Scholar : PubMed/NCBI
18	Yang XW, Shen GZ, Cao LQ, Jiang XF, Peng HP, Shen G, Chen D and Xue P: MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1. BMC Cancer. 14:9092014. View Article : Google Scholar : PubMed/NCBI
19	Png KJ, Yoshida M, Zhang XH, Shu W, Lee H, Rimner A, Chan TA, Comen E, Andrade VP, Kim SW, et al: MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes Dev. 25:226–231. 2011. View Article : Google Scholar : PubMed/NCBI
20	Gao X and Jin W: The emerging role of tumor-suppressive microRNA-218 in targeting glioblastoma stemness. Cancer Lett. 353:25–31. 2014. View Article : Google Scholar : PubMed/NCBI
21	Jiang J, Zhang Y, Yu C, Li Z, Pan Y and Sun C: MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN. Cancer Cell Int. 14:952014. View Article : Google Scholar : PubMed/NCBI
22	Denoyelle C, Lambert B, Meryet-Figuière M, Vigneron N, Brotin E, Lecerf C, Abeilard E, Giffard F, Louis MH, Gauduchon P, et al: miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation. Cell Death Dis. 5:e14452014. View Article : Google Scholar : PubMed/NCBI
23	Yonemori K, Kurahara H, Maemura K and Natsugoe S: MicroRNA in pancreatic cancer. J Hum Genet. 62:33–40. 2017. View Article : Google Scholar : PubMed/NCBI
24	Lv Y, Lei Y, Hu Y, Ding W, Zhang C and Fang C: miR-448 negatively regulates ovarian cancer cell growth and metastasis by targeting CXCL12. Clin Transl Oncol. 17:903–909. 2015. View Article : Google Scholar : PubMed/NCBI
25	Li QQ, Chen ZQ, Cao XX, Xu JD, Xu JW, Chen YY, Wang WJ, Chen Q, Tang F, Liu XP, et al: Involvement of NF-κB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells. Cell Death Differ. 18:16–25. 2011. View Article : Google Scholar : PubMed/NCBI
26	Wu X, Tang H, Liu G, Wang H, Shu J and Sun F: miR-448 suppressed gastric cancer proliferation and invasion by regulating ADAM10. Tumour Biol. 37:10545–10551. 2016. View Article : Google Scholar : PubMed/NCBI
27	Li B, Ge L, Li M, Wang L and Li Z: miR-448 suppresses proliferation and invasion by regulating IGF1R in colorectal cancer cells. Am J Transl Res. 8:3013–3022. 2016.PubMed/NCBI
28	Shen L, Liu L, Ge L, Xie L, Liu S, Sang L, Zhan T and Li H: miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit apoptosis in oral squamous cell carcinoma. Exp Ther Med. 12:2747–2752. 2016.PubMed/NCBI
29	Zhu H, Zhou X, Ma C, Chang H, Li H, Liu F and Lu J: Low expression of miR-448 induces EMT and promotes invasion by regulating ROCK2 in hepatocellular carcinoma. Cell Physiol Biochem. 36:487–498. 2015. View Article : Google Scholar : PubMed/NCBI
30	Mendonsa AM, VanSaun MN, Ustione A, Piston DW, Fingleton BM and Gorden DL: Host and tumor derived MMP13 regulate extravasation and establishment of colorectal metastases in the liver. Mol Cancer. 14:492015. View Article : Google Scholar : PubMed/NCBI
31	Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR, et al: A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 14:1421–1429. 1995.PubMed/NCBI
32	Verma A, Kambhampati S, Parmar S and Platanias LC: Jak family of kinases in cancer. Cancer Metastasis Rev. 22:423–434. 2003. View Article : Google Scholar : PubMed/NCBI
33	Yuan J, Ji H, Xiao F, Lin Z, Zhao X, Wang Z, Zhao J and Lu J: MicroRNA-340 inhibits the proliferation and invasion of hepatocellular carcinoma cells by targeting JAK1. Biochem Biophys Res Commun. 483:578–584. 2017. View Article : Google Scholar : PubMed/NCBI
34	Liu D, Huang Y, Zeng J, Chen B, Huang N, Guo N, Liu L, Xu H, Mo X and Li W: Down-regulation of JAK1 by RNA interference inhibits growth of the lung cancer cell line A549 and interferes with the PI3K/mTOR pathway. J Cancer Res Clin Oncol. 137:1629–1640. 2011. View Article : Google Scholar : PubMed/NCBI
35	Xiong H, Zhang ZG, Tian XQ, Sun DF, Liang QC, Zhang YJ, Lu R, Chen YX and Fang JY: Inhibition of JAK1, 2/STAT3 signaling induces apoptosis, cell cycle arrest, and reduces tumor cell invasion in colorectal cancer cells. Neoplasia. 10:287–297. 2008. View Article : Google Scholar : PubMed/NCBI