Knockdown of long non‑coding RNA DDX11‑AS1 inhibits the proliferation, migration and paclitaxel resistance of breast cancer cells by upregulating microRNA‑497 expression

Liang,Meng; Zhu,Beibei; Wang,Min; Jin,Ju

doi:10.3892/mmr.2022.12639

Knockdown of long non‑coding RNA DDX11‑AS1 inhibits the proliferation, migration and paclitaxel resistance of breast cancer cells by upregulating microRNA‑497 expression

Authors:
- Meng Liang
- Beibei Zhu
- Min Wang
- Ju Jin
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Affiliations: Department of Pathology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Jinan University, Guangdong, Guangzhou 510632, P.R. China, Emergency Department, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China, Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, P.R. China
Published online on: February 11, 2022 https://doi.org/10.3892/mmr.2022.12639
Article Number: 123
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Drug resistance is a major problem to overcome in the treatment of cancer; therefore, identifying therapeutic targets for drug resistance is a point of focus in the field of cancer research. Long non‑coding RNAs (lncRNAs) and microRNAs (miRs) not only affect gene expression regulation during cell proliferation, but also have several potential roles in the drug resistance of malignant tumors. Reverse transcription‑quantitative PCR was used to detect the expression levels of DDX11 antisense RNA 1 (DDX11‑AS1) and miR‑497 in MCF‑7 and MDA‑MB‑231 cells. Cell transfection techniques were used to interfere with the expression levels of DDX11‑AS1 and miR‑497. Cell Counting Kit‑8 and MTT assays were used to detect cell viability. A colony formation assay was used to detect cell proliferation. Wound‑healing and Transwell assays were performed to measure the levels of cell migration and invasion. Western blotting was used to analyze the expression levels of migration‑associated proteins, and immunofluorescence and western blotting were used to determine the expression levels of the epithelial‑mesenchymal transition‑related proteins E‑cadherin and N‑cadherin, respectively. A luciferase reporter gene assay was used to verify the targeted binding of DDX11‑AS1 and miR‑497. The present study demonstrated that the expression levels of lncRNA DDX11‑AS1 were markedly increased in paclitaxel (PTX)‑resistant breast cancer cell lines. By contrast, knockdown of DDX11‑AS1 expression inhibited PTX resistance of breast cancer cells, and suppressed the proliferation, invasion and migration of breast cancer cells, which was achieved via upregulation of miR‑497 expression. In conclusion, knockdown of lncRNA DDX11‑AS1 could inhibit the proliferation, migration and PTX resistance of breast cancer cells by upregulating miR‑497 expression.

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1	Bevers TB, Helvie M, Bonaccio E, Calhoun KE, Daly MB, Farrar WB, Garber JE, Gray R, Greenberg CC, Greenup R, et al: Breast cancer screening and diagnosis, version 3.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 16:1362–1389. 2018. View Article : Google Scholar : PubMed/NCBI
2	Falzone L, Salomone S and Libra M: Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol. 9:13002018. View Article : Google Scholar : PubMed/NCBI
3	Christofi T, Baritaki S, Falzone L, Libra M and Zaravinos A: Current perspectives in cancer immunotherapy. Cancers (Basel). 11:14722019. View Article : Google Scholar : PubMed/NCBI
4	Tong CWS, Wu M, Cho WCS and To KKW: Recent advances in the treatment of breast cancer. Front Oncol. 8:2272018. View Article : Google Scholar : PubMed/NCBI
5	Mustacchi G and De Laurentiis M: The role of taxanes in triple-negative breast cancer: Literature review. Drug Des Devel Ther. 9:4303–4318. 2015. View Article : Google Scholar : PubMed/NCBI
6	Telli M: Evolving treatment strategies for triple-negative breast cancer. J Natl Compr Canc Netw. 13 (Suppl 5):S652–S654. 2015. View Article : Google Scholar : PubMed/NCBI
7	Xu J, Wu KJ, Jia QJ and Ding XF: Roles of miRNA and lncRNA in triple-negative breast cancer. J Zhejiang Univ Sci B. 21:673–689. 2020. View Article : Google Scholar : PubMed/NCBI
8	Mattick JS and Makunin IV: Non-coding RNA. Hum Mol Genet. 15:Spec No: 1. R17–R29. 2006. View Article : Google Scholar : PubMed/NCBI
9	Liz J and Esteller M: lncRNAs and microRNAs with a role in cancer development. Biochim Biophys Acta. 1859:169–176. 2016. View Article : Google Scholar : PubMed/NCBI
10	Polo A, Crispo A, Cerino P, Falzone L, Candido S, Giudice A, Petro GD, Ciliberto G, Montella M, Budillon A and Costantini S: Environment and bladder cancer: Molecular analysis by interaction networks. Oncotarget. 8:65240–65252. 2017. View Article : Google Scholar : PubMed/NCBI
11	Falzone L, Grimaldi M, Celentano E, Augustin LSA and Libra M: Identification of modulated MicroRNAs associated with breast cancer, diet, and physical activity. Cancers (Basel). 12:25552020. View Article : Google Scholar : PubMed/NCBI
12	Soudyab M, Iranpour M and Ghafouri-Fard S: The role of long non-coding RNAs in breast cancer. Arch Iran Med. 19:508–517. 2016.PubMed/NCBI
13	Tian JB, Cao L and Dong GL: Long noncoding RNA DDX11-AS1 induced by YY1 accelerates colorectal cancer progression through targeting miR-873/CLDN7 axis. Eur Rev Med Pharmacol Sci. 23:5714–5729. 2019.PubMed/NCBI
14	Zhang S, Jiang H, Xu Z, Jiang Y, She Y, Huang X, Feng S, Chen W, Chen S, Chen Y, et al: The resistance of esophageal cancer cells to paclitaxel can be reduced by the knockdown of long noncoding RNA DDX11-AS1 through TAF1/TOP2A inhibition. Am J Cancer Res. 9:2233–2248. 2019.PubMed/NCBI
15	Wu Z, Cai X, Huang C, Xu J and Liu A: miR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1α. Oncol Rep. 35:1696–1702. 2016. View Article : Google Scholar : PubMed/NCBI
16	Tian F, Zhan Y, Zhu W, Li J, Tang M, Chen X and Jiang J: MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2. Int J Mol Med. 43:1058–1066. 2019.PubMed/NCBI
17	Liu Z, Wu S, Wang L, Kang S, Zhao B, He F, Liu X, Zeng Y and Liu J: Prognostic value of microRNA-497 in various cancers: A systematic review and meta-analysis. Dis Markers. 2019:24912912019. View Article : Google Scholar : PubMed/NCBI
18	Luo G, He K, Xia Z, Liu S, Liu H and Xiang G: Regulation of microRNA-497 expression in human cancer. Oncol Lett. 21:232021.PubMed/NCBI
19	Xu S, Fu GB, Tao Z, OuYang J, Kong F, Jiang BH, Wan X and Chen K: miR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1. Oncotarget. 6:26457–26471. 2015. View Article : Google Scholar : PubMed/NCBI
20	Panayotopoulou EG, Müller AK, Borries M, Busch H, Hu G and Lev S: Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxel-resistant triple negative breast cancer cells. Oncotarget. 8:45088–45104. 2017. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Chen Z, Lin T, Liao X, Li Z, Lin R, Qi X, Chen G, Sun L and Lin L: Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma. Chin Med. 16:132021. View Article : Google Scholar : PubMed/NCBI
23	Hassan MS, Ansari J, Spooner D and Hussain SA: Chemotherapy for breast cancer (Review). Oncol Rep. 24:1121–1131. 2010. View Article : Google Scholar : PubMed/NCBI
24	Chun KH, Park JH and Fan S: Predicting and overcoming chemotherapeutic resistance in breast cancer. Adv Exp Med Biol. 1026:59–104. 2017. View Article : Google Scholar : PubMed/NCBI
25	Malhotra A, Jain M, Prakash H, Vasquez KM and Jain A: The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer. Oncotarget. 8:110671–110684. 2017. View Article : Google Scholar : PubMed/NCBI
26	Li Y, Zhuang W, Huang M and Li X: Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular carcinoma. Biochem Biophys Res Commun. 514:1051–1057. 2019. View Article : Google Scholar : PubMed/NCBI
27	Chen D, Chen J, Gao J, Zhang Y, Ma Y, Wei W and Wei Y: LncRNA DDX11-AS1 promotes bladder cancer occurrence via protecting LAMB3 from downregulation by sponging miR-2355-5p. Cancer Biother Radiopharm. 35:319–328. 2020. View Article : Google Scholar : PubMed/NCBI
28	Pang PC, Shi XY, Huang WL and Sun K: miR-497 as a potential serum biomarker for the diagnosis and prognosis of osteosarcoma. Eur Rev Med Pharmacol Sci. 20:3765–3769. 2016.PubMed/NCBI
29	Chai L, Kang XJ, Sun ZZ, Zeng MF, Yu SR, Ding Y, Liang JQ, Li TT and Zhao J: miR-497-5p, miR-195-5p and miR-455-3p function as tumor suppressors by targeting hTERT in melanoma A375 cells. Cancer Manag Res. 10:989–1003. 2018. View Article : Google Scholar : PubMed/NCBI
30	Wei XH, Gu XL, Zhou XT, Ma M and Lou CX: miR-497 promotes the progression of cutaneous squamous cell carcinoma through FAM114A2. Eur Rev Med Pharmacol Sci. 22:7348–7355. 2018.PubMed/NCBI
31	Zhong H, Yang J, Zhang B, Wang X, Pei L, Zhang L, Lin Z, Wang Y and Wang C: LncRNA GACAT3 predicts poor prognosis and promotes cell proliferation in breast cancer through regulation of miR-497/CCND2. Cancer Biomark. 22:787–797. 2018. View Article : Google Scholar : PubMed/NCBI
32	Bai J, Zhao WY, Li WJ, Ying ZW and Jiang DQ: Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497. Eur Rev Med Pharmacol Sci. 23:3410–3420. 2019.PubMed/NCBI
33	Zhu D, Tu M, Zeng B, Cai L, Zheng W, Su Z and Yu Z: Up-regulation of miR-497 confers resistance to temozolomide in human glioma cells by targeting mTOR/Bcl-2. Cancer Med. 6:452–462. 2017. View Article : Google Scholar : PubMed/NCBI