Long non‑coding RNA ENST00000500843 is downregulated and promotes chemoresistance to paclitaxel in lung adenocarcinoma

Tian,Xin; Gao,Song; Liu,Yang; Xuan,Ying; Wu,Rong; Zhang,Zhenyong

doi:10.3892/ol.2019.10704

Long non‑coding RNA ENST00000500843 is downregulated and promotes chemoresistance to paclitaxel in lung adenocarcinoma

Authors:
- Xin Tian
- Song Gao
- Yang Liu
- Ying Xuan
- Rong Wu
- Zhenyong Zhang
View Affiliations

Affiliations: Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: August 2, 2019 https://doi.org/10.3892/ol.2019.10704
Pages: 3716-3722
Copyright : © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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

Adenocarcinoma is one of the most common pathological types of human lung cancer and has the highest incidence and mortality rates worldwide. Resistance to paclitaxel (PTX), the standard chemotherapy agent for treatment of lung adenocarcinoma, is a major clinical obstacle. Sensitive markers are urgently required for the diagnosis and characterization of lung cancer, as well as to manage drug resistance. Previous studies have described the activity of long non‑coding RNAs (lncRNAs) in human lung cancer and chemotherapy resistance. In previous studies, lncRNA ENST00000500843 was identified to be downregulated in PTX‑resistant A549 human lung cancer cells. However, the roles of this lncRNA in the development of lung adenocarcinoma and its mechanism in PTX resistance, to the best of our knowledge, have not been described. In the present study, 56 pairs of lung adenocarcinoma and normal adjacent tissue samples were collected. Reverse transcription‑quantitative PCR revealed that the expression levels of lncRNA ENST00000500843 were lower in lung adenocarcinoma tissues and PTX‑resistant A549 cells when compared with normal adjacent tissues and A549 cells. Decreased expression levels of lncRNA ENST00000500843 in lung adenocarcinoma tissues were associated with tumor diameter, the degree of pathological differentiation and metastasis of lymph nodes. Additionally, patients with low expression levels of ENST00000500843 exhibited poorer overall survival and progression‑free survival rates. Furthermore, the present study demonstrated that knockdown of lncRNA ENST00000500843 with small interfering RNA decreased the likelihood of apoptosis in A549 cells and promoted resistance to PTX. This indicated that lncRNA ENST00000500843 may be a useful diagnostic marker of lung cancer and a good prognostic marker for resistance to treatment with PTX.

View Figures

View References

1	Jochems A, El-Naqa I, Kessler M, Mayo CS, Jolly S, Matuszak M, Faivre-Finn C, Price G, Holloway L, Vinod S, et al: A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy. Acta Oncol. 57:226–230. 2018. View Article : Google Scholar : PubMed/NCBI
2	Roengvoraphoj O, Wijaya C, Eze C, Li M, Dantes M, Taugner J, Tufman A, Huber RM, Belka C and Manapov F: Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer. Strahlenther Onkol. 194:107–115. 2018. View Article : Google Scholar : PubMed/NCBI
3	Guilbault C, Garant A, Faria S, Owen S, Ofiara L, Duclos M, Hirsh V and Kopek N: Long-term outcomes of induction carboplatin and gemcitabine followed by concurrent radiotherapy with low-dose paclitaxel and gemcitabine for stage III non-small-cell lung cancer. Clin Lung Cancer. 18:565–571. 2017. View Article : Google Scholar : PubMed/NCBI
4	Morgensztern D, Ng SH, Gao F and Govindan R: Trends in stage distribution for patients with non-small cell lung cancer: A National Cancer Database survey. J Thorac Oncol. 5:29–33. 2010. View Article : Google Scholar : PubMed/NCBI
5	Jiang N, Dong XP, Zhang SL, You QY, Jiang XT and Zhao XG: Triptolide reverses the Taxol resistance of lung adenocarcinoma by inhibiting the NF-κB signaling pathway and the expression of NF-κB-regulated drug-resistant genes. Mol Med Rep. 13:153–159. 2016. View Article : Google Scholar : PubMed/NCBI
6	Liu R, Liu X, Zheng Y, Gu J, Xiong S, Jiang P, Jiang X, Huang E, Yang Y, Ge D and Chu Y: MicroRNA-7 sensitizes non-small cell lung cancer cells to paclitaxel. Oncol Lett. 8:2193–2200. 2014. View Article : Google Scholar : PubMed/NCBI
7	Holleman A, Chung I, Olsen RR, Kwak B, Mizokami A, Saijo N, Parissenti A, Duan Z, Voest EE and Zetter BR: miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene. 30:4386–4398. 2011. View Article : Google Scholar : PubMed/NCBI
8	Datta S, Choudhury D, Das A, Das Mukherjee D, Das N, Roy SS and Chakrabarti G: Paclitaxel resistance development is associated with biphasic changes in reactive oxygen species, mitochondrial membrane potential and autophagy with elevated energy production capacity in lung cancer cells: A chronological study. Tumour Biol. 39:10104283176943142017. View Article : Google Scholar : PubMed/NCBI
9	Sun QL, Sha HF, Yang XH, Bao GL, Lu J and Xie YY: Comparative proteomic analysis of paclitaxel sensitive A549 lung adenocarcinoma cell line and its resistant counterpart A549-taxol. J Cancer Res Clin Oncol. 137:521–532. 2011. View Article : Google Scholar : PubMed/NCBI
10	Azuma Y, Yokobori T, Mogi A, Altan B, Yajima T, Kosaka T, Onozato R, Yamaki E, Asao T, Nishiyama M and Kuwano H: SIRT6 expression is associated with poor prognosis and chemosensitivity in patients with non-small cell lung cancer. J Surg Oncol. 112:231–237. 2015. View Article : Google Scholar : PubMed/NCBI
11	Yang Y, Li H, Hou S, Hu B, Liu J and Wang J: The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 8:e653092013. View Article : Google Scholar : PubMed/NCBI
12	Li Z, Zhao X, Zhou Y, Liu Y, Zhou Q, Ye H, Wang Y, Zeng J, Song Y, Gao W, et al: The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer. J Transl Med. 13:842015. View Article : Google Scholar : PubMed/NCBI
13	Liu B, Pan CF, Ma T, Wang J, Yao GL, Wei K and Chen YJ: Long non-coding RNA AK001796 contributes to cisplatin resistance of non-small cell lung cancer. Mol Med Rep. 16:4107–4112. 2017. View Article : Google Scholar : PubMed/NCBI
14	Lee H, Kim C, Ku JL, Kim W, Yoon SK, Kuh HJ, Lee JH, Nam SW and Lee EK: A long non-coding RNA snaR contributes to 5-fluorouracil resistance in human colon cancer cells. Mol Cells. 37:540–546. 2014. View Article : Google Scholar : PubMed/NCBI
15	Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, De W, Wang Z and Wang R: The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 8:e772932013. View Article : Google Scholar : PubMed/NCBI
16	Dong S, Qu X, Li W, Zhong X, Li P, Yang S, Chen X, Shao M and Zhang L: The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 8:432015. View Article : Google Scholar : PubMed/NCBI
17	Shi Y, Lv C, Shi L and Tu G: MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells. Oncol Lett. 15:1917–1923. 2018.PubMed/NCBI
18	Xia Y, He Z, Liu B, Wang P and Chen Y: Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/β-catenin signaling pathway. Mol Med Rep. 12:4530–4537. 2015. View Article : Google Scholar : PubMed/NCBI
19	Liu J, Wan L, Lu K, Sun M, Pan X, Zhang P, Lu B, Liu G and Wang Z: The long noncoding RNA MEG3 contributes to cisplatin resistance of human lung adenocarcinoma. PLoS One. 10:e01145862015. View Article : Google Scholar : PubMed/NCBI
20	Tian X, Zhang H, Zhang B, Zhao J, Li T and Zhao Y: Microarray expression profile of long non-coding RNAs in paclitaxel-resistant human lung adenocarcinoma cells. Oncol Rep. 38:293–300. 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	Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, et al: American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual. 8th. Springer; New York, NY: 2017, View Article : Google Scholar
23	Jiang B, Liu J, Zhang YH, Shen D, Liu S, Lin F, Su J, Lin QF, Yan S, Li Y, et al: Long noncoding RNA LINC00961 inhibits cell invasion and metastasis in human non-small cell lung cancer. Biomed Pharmacother. 97:1311–1318. 2018. View Article : Google Scholar : PubMed/NCBI
24	Zhang W, Yuan W, Song J, Wang S and Gu X: lncRna CPS1-IT1 suppresses cell proliferation, invasion and metastasis in colorectal cancer. Cell Physiol Biochem. 44:567–580. 2017. View Article : Google Scholar : PubMed/NCBI
25	Li J, Zhang M, An G and Ma Q: lncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis. Exp Biol Med (Maywood). 241:644–649. 2016. View Article : Google Scholar : PubMed/NCBI
26	Luo Y, Xuan Z, Zhu X, Zhan P and Wang Z: Long non-coding RNAs RP5-821D11.7, APCDD1L-AS1 and RP11-277P12.9 were associated with the prognosis of lung squamous cell carcinoma. Mol Med Rep. 17:7238–7248. 2018.PubMed/NCBI
27	Chen Y, Wei G, Xia H, Tang Q and Bi F: Long noncoding RNA-ATB promotes cell proliferation, migration and invasion in gastric cancer. Mol Med Rep. 17:1940–1946. 2018.PubMed/NCBI
28	Ding J, Li D, Gong M, Wang J, Huang X, Wu T and Wang C: Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer. Onco Targets Ther. 7:1625–1630. 2014. View Article : Google Scholar : PubMed/NCBI
29	Ren K, Xu R, Huang J, Zhao J and Shi W: Knockdown of long non-coding RNA KCNQ1OT1 depressed chemoresistance to paclitaxel in lung adenocarcinoma. Cancer Chemother Pharmacol. 80:243–250. 2017. View Article : Google Scholar : PubMed/NCBI
30	Wang Q, Zhang W and Hao S: lncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis. Cell Cycle. 16:795–801. 2017. View Article : Google Scholar : PubMed/NCBI
31	Ren S, Li G, Liu C, Cai T, Su Z, Wei M, She L, Tian Y, Qiu Y, Zhang X, et al: Next generation deep sequencing identified a novel lncRNA n375709 associated with paclitaxel resistance in nasopharyngeal carcinoma. Oncol Rep. 36:1861–1867. 2016. View Article : Google Scholar : PubMed/NCBI
32	Xu J, Wu J, Fu C, Teng F, Liu S, Dai C, Shen R and Jia X: Multidrug resistant lncRNA profile inchemotherapeutic sensitive and resistant ovarian cancer cells. J Cell Physiol. 233:5034–5043. 2018. View Article : Google Scholar : PubMed/NCBI