Chronic oxymatrine treatment induces resistance and epithelial‑mesenchymal transition through targeting the long 
non-coding RNA MALAT1 in colorectal cancer cells Retraction in /10.3892/or.2024.8732

Xiong,Yibai; Wang,Jun; Zhu,Huirong; Liu,Lingshuang; Jiang,Yi

doi:10.3892/or.2018.6204

Chronic oxymatrine treatment induces resistance and epithelial‑mesenchymal transition through targeting the long non-coding RNA MALAT1 in colorectal cancer cells

Retraction in: /10.3892/or.2024.8732

Authors:
- Yibai Xiong
- Jun Wang
- Huirong Zhu
- Lingshuang Liu
- Yi Jiang
View Affiliations

Affiliations: Department of Oncology, Longhua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200021, P.R. China, Department of Anorectal Surgery, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China, Shanghai University of Traditional Chinese Medicine, Shanghai 200021, P.R. China
Published online on: January 10, 2018 https://doi.org/10.3892/or.2018.6204
Pages: 967-976
Copyright: © Xiong 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

A major reason for colorectal cancer (CRC) chemoresistance is the enhanced migration and invasion of cancer cells, such as the cell acquisition of epithelial-mesenchymal transition (EMT). Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been considered as a pro-oncogene in multiple cancers. However, the precise functional mechanism of lncRNA MALAT1 in chemoresistance and EMT is not well known. In the present study, we focused on the effect of oxymatrine on CRC cells and further investigated the role of MALAT1 in oxymatrine-induced resistance and EMT process. The human CRC cell line HT29 was exposed to increasing doses of oxymatrine to establish stable cell lines resistant to oxymatrine. The established HT29 oxymatrine resistant cells showed an EMT phenotype including specific morphologic changes, enhanced migratory and invasive capacity, and downregulation of E-cadherin protein expression. Subsequently, high-throughput HiSeq sequencing and RT-qPCR showed that lncRNA MALAT1 was significantly upregulated in the oxymatrine resistant cells (P<0.01), while knockdown of MALAT1 partially reversed the EMT phenotype in HT29 resistant cells. Furthermore, oxymatrine treatment suppressed the migration and invasion ability of CRC cells, however, this effect was significantly reversed by overexpression of MALAT1. Finally, we investigated the clinical role of MALAT1 and found that high lncRNA MALAT1 expression level is associated with poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01). In conclusion, we demonstrate that lncRNA MALAT1 is a stimulator for oxymatrine resistance in CRC and it may provide therapeutic and prognostic information for CRC patients.

View Figures

View References

1	Han D, Wang M, Ma N, Xu Y, Jiang Y and Gao X: Long non-coding RNAs: Novel players in colorectal cancer. Cancer Lett. 361:13–21. 2015. View Article : Google Scholar : PubMed/NCBI
2	Li PL, Zhang X, Wang LL, Du LT, Yang YM, Li J and Wang CX: MicroRNA-218 is a prognostic indicator in colorectal cancer and enhances 5-fluorouracil-induced apoptosis by targeting BIRC5. Carcinogenesis. 36:1484–1493. 2015.PubMed/NCBI
3	Tomida C, Aibara K, Yamagishi N, Yano C, Nagano H, Abe T, Ohno A, Hirasaka K, Nikawa T and Teshima-Kondo S: The malignant progression effects of regorafenib in human colon cancer cells. J Med Invest. 62:195–198. 2015. View Article : Google Scholar : PubMed/NCBI
4	Alberts SR, Horvath WL, Sternfeld WC, Goldberg RM, Mahoney MR, Dakhil SR, Levitt R, Rowland K, Nair S, Sargent DJ, et al: Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: A North Central Cancer Treatment Group phase II study. J Clin Oncol. 23:9243–9249. 2005. View Article : Google Scholar : PubMed/NCBI
5	Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC and Alberts SR: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 22:23–30. 2004. View Article : Google Scholar : PubMed/NCBI
6	Yamauchi K, Yang M, Hayashi K, Jiang P, Yamamoto N, Tsuchiya H, Tomita K, Moossa AR, Bouvet M and Hoffman RM: Induction of cancer metastasis by cyclophosphamide pretreatment of host mice: An opposite effect of chemotherapy. Cancer Res. 68:516–520. 2008. View Article : Google Scholar : PubMed/NCBI
7	Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, Chen ZQ, Liu XP and Xu ZD: Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 15:2657–2665. 2009. View Article : Google Scholar : PubMed/NCBI
8	Li-Weber M: Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Lett. 332:304–312. 2013. View Article : Google Scholar : PubMed/NCBI
9	Zhang MJ and Huang J: Recent research progress of anti-tumor mechnism matrine. Zhongguo Zhong Yao Za Zhi. 29:115–118. 2004.(In Chinese). PubMed/NCBI
10	Liang L and Huang J: Oxymatrine inhibits epithelial-mesenchymal transition through regulation of NF-κB signaling in colorectal cancer cells. Oncol Rep. 36:1333–1338. 2016. View Article : Google Scholar : PubMed/NCBI
11	Fei ZW, Qiu MK, Qi XQ, Dai YX, Wang SQ, Quan ZW, Liu YB and Ou JM: Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling. Int J Immunopathol Pharmacol. 28:201–208. 2015. View Article : Google Scholar : PubMed/NCBI
12	Chen H, Zhang J, Luo J, Lai F, Wang Z, Tong H, Lu D, Bu H, Zhang R and Lin S: Antiangiogenic effects of oxymatrine on pancreatic cancer by inhibition of the NF-κB-mediated VEGF signaling pathway. Oncol Rep. 30:589–595. 2013. View Article : Google Scholar : PubMed/NCBI
13	Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, et al: RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 316:1484–1488. 2007. View Article : Google Scholar : PubMed/NCBI
14	Pang EJ, Yang R, Fu XB and Liu YF: Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 36:2403–2407. 2015. View Article : Google Scholar : PubMed/NCBI
15	Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, Wei M, Xu C, Wu C, Zhang Z, et al: Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 49:2949–2959. 2013. View Article : Google Scholar : PubMed/NCBI
16	Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, et al: MALAT-1, a novel non-coding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
17	Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F and Liu Y: TGF-β-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin Cancer Res. 20:1531–1541. 2014. View Article : Google Scholar : PubMed/NCBI
18	Hirata H, Hinoda Y, Shahryari V, Deng G, Nakajima K, Tabatabai ZL, Ishii N and Dahiya R: Long non-coding RNA MALAT1 promotes aggressive renal cell carcinoma through Ezh2 and interacts with miR-205. Cancer Res. 75:1322–1331. 2015. View Article : Google Scholar : PubMed/NCBI
19	Qi Y, Ooi HS, Wu J, Chen J, Zhang X, Tan S, Yu Q, Li YY, Kang Y, Li H, et al: MALAT1 long ncRNA promotes gastric cancer metastasis by suppressing PCDH10. Oncotarget. 7:12693–12703. 2016. View Article : Google Scholar : PubMed/NCBI
20	Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J, et al: Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS One. 8:e787002013. View Article : Google Scholar : PubMed/NCBI
21	Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, et al: The landscape of long non-coding RNAs in the human transcriptome. Nat Genet. 47:199–208. 2015. View Article : Google Scholar : PubMed/NCBI
22	Yang AD, Fan F, Camp ER, van Buren G, Liu W, Somcio R, Gray MJ, Cheng H, Hoff PM and Ellis LM: Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res. 12:4147–4153. 2006. View Article : Google Scholar : PubMed/NCBI
23	Li P, Zhang X, Wang H, Wang L, Liu T, Du L, Yang Y and Wang C: MALAT1 is associated with poor response to oxaliplatin-based chemotherapy in colorectal cancer patients and promotes chemoresistance through EZH2. Mol Cancer Ther. 16:739–751. 2017. View Article : Google Scholar : PubMed/NCBI
24	Cho SF, Chang YC, Chang CS, Lin SF, Liu YC, Hsiao HH, Chang JG and Liu TC: MALAT1 long non-coding RNA is overexpressed in multiple myeloma and may serve as a marker to predict disease progression. BMC Cancer. 14:8092014. View Article : Google Scholar : PubMed/NCBI
25	Ren S, Liu Y, Xu W, Sun Y, Lu J, Wang F, Wei M, Shen J, Hou J, Gao X, et al: Long non-coding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol. 190:2278–2287. 2013. View Article : Google Scholar : PubMed/NCBI
26	Gong W, Wang Z, Wan Y, Shi L and Zhou Y: Downregulation of ABCG2 protein inhibits migration and invasion in U251 glioma stem cells. Neuroreport. 25:625–632. 2014. View Article : Google Scholar : PubMed/NCBI
27	Wang B, Han Q and Zhu Y: Oxymatrine inhibited cell proliferation by inducing apoptosis in human lung cancer A549 cells. Biomed Mater Eng. 26 Suppl 1:S165–S172. 2015.PubMed/NCBI
28	Guo B, Zhang T, Su J, Wang K and Li X: Oxymatrine targets EGFR^p-Tyr845 and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells. Cancer Chemother Pharmacol. 75:353–363. 2015. View Article : Google Scholar : PubMed/NCBI
29	Ling Q, Xu X, Wei X, Wang W, Zhou B, Wang B and Zheng S: Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome c. J Exp Clin Cancer Res. 30:662011. View Article : Google Scholar : PubMed/NCBI
30	Zhang Y, Piao B, Zhang Y, Hua B, Hou W, Xu W, Qi X, Zhu X, Pei Y and Lin H: Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells. Med Oncol. 28 Suppl 1:S99–S107. 2011. View Article : Google Scholar : PubMed/NCBI
31	Hector S, Bolanowska-Higdon W, Zdanowicz J, Hitt S and Pendyala L: In vitro studies on the mechanisms of oxaliplatin resistance. Cancer Chemother Pharmacol. 48:398–406. 2001. View Article : Google Scholar : PubMed/NCBI
32	Samimi G, Manorek G, Castel R, Breaux JK, Cheng TC, Berry CC, Los G and Howell SB: cDNA microarray-based identification of genes and pathways associated with oxaliplatin resistance. Cancer Chemother Pharmacol. 55:1–11. 2005. View Article : Google Scholar : PubMed/NCBI
33	Gutschner T, Hämmerle M and Diederichs S: MALAT1 - a paradigm for long non-coding RNA function in cancer. J Mol Med. 91:791–801. 2013. View Article : Google Scholar : PubMed/NCBI
34	Chen W, Xu XK, Li JL, Kong KK, Li H, Chen C, He J, Wang F, Li P, Ge XS, et al: MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression. Oncotarget. 8:22783–22799. 2017.PubMed/NCBI
35	Yuan P, Cao W, Zang Q, Li G, Guo X and Fan J: The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy. Biochem Biophys Res Commun. 478:1067–1073. 2016. View Article : Google Scholar : PubMed/NCBI
36	Cao X, Zhao R, Chen Q, Zhao Y, Zhang B, Zhang Y, Yu J, Han G, Cao W, Li J, et al: MALAT1 might be a predictive marker of poor prognosis in patients who underwent radical resection of middle thoracic esophageal squamous cell carcinoma. Cancer Biomark. 15:717–723. 2015. View Article : Google Scholar : PubMed/NCBI
37	Liu M, Sun W, Liu Y and Dong X: The role of lncRNA MALAT1 in bone metastasis in patients with non-small cell lung cancer. Oncol Rep. 36:1679–1685. 2016. View Article : Google Scholar : PubMed/NCBI