Long non‑coding RNA BCYRN1 promotes glycolysis and tumor progression by regulating the miR‑149/PKM2 axis in non‑small‑cell lung cancer Retraction in /10.3892/mmr.2024.13380

Lang,Ning; Wang,Chunyang; Zhao,Jiangyang; Shi,Feng; Wu,Tong; Cao,Hongyan

doi:10.3892/mmr.2020.10944

Long non‑coding RNA BCYRN1 promotes glycolysis and tumor progression by regulating the miR‑149/PKM2 axis in non‑small‑cell lung cancer

Retraction in: /10.3892/mmr.2024.13380

Authors:
- Ning Lang
- Chunyang Wang
- Jiangyang Zhao
- Feng Shi
- Tong Wu
- Hongyan Cao
View Affiliations

Affiliations: Department of Preventive Health, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Thoracic Surgery, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China, Department of Respiratory Diseases, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China, Department of Oncology, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
Published online on: January 16, 2020 https://doi.org/10.3892/mmr.2020.10944
Pages: 1509-1516
Copyright: © Lang 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

Cancer cells use aerobic glycolysis to sustain their proliferation. Long non‑coding RNA brain cytoplasmic RNA 1 (BCYRN1) has been reported to act as an oncogene in non‑small‑cell lung cancer (NSCLC). The present study investigated the role of BCYRN1 in NSCLC glycolysis. BCYRN1 expression was detected in NSCLC cells and tissues using reverse transcription‑quantitative PCR. The effect of BCYRN1 on aerobic glycolysis was examined by measuring NSCLC cell glucose catabolism and lactate synthesis. The relationships between BCYRN1 and microRNA (miR)‑149, and between miR‑149 and pyruvate kinase M1/2 (PKM2) were measured using a dual‑luciferase reporter assay. Cell proliferation and invasion were analyzed by the Cell Counting kit‑8 assay and the Matrigel invasion assay, respectively. High BCYRN1 expression was observed in NSCLC tissues and cells compared with the corresponding controls. BCYRN1 induced glycolysis and upregulated the expression levels of PKM2 in NSCLC cells. In addition, BCYRN1 regulated miR‑149 expression levels, and miR‑149 inhibitor rescued the effects of si‑BCYRN1 on glucose consumption and lactate production. miR‑149 knockdown significantly enhanced the expression of PKM2. Furthermore, PKM2 inhibition significantly reversed the effects of miR‑149 inhibitor on glucose catabolism and lactate synthesis. Furthermore, PKM2 was involved in NSCLC cell proliferation and invasion, and BCYRN1 knockdown and miR‑149 overexpression inhibited both processes. The present study suggested that BCYRN1 was involved in cell glycolysis, proliferation and invasion during NSCLC via regulating miR‑149 and PKM2.

View Figures

View References

1	Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, Shafi S, Johnson DH, Mitter R, Rosenthal R, et al: Tracking the evolution of non-small-cell lung cancer. N Engl J Med. 376:2109–2121. 2017. View Article : Google Scholar : PubMed/NCBI
2	Detterbeck FC, Boffa DJ, Kim AW and Tanoue LT: The eighth edition lung cancer stage classification. Chest. 151:193–203. 2017. View Article : Google Scholar : PubMed/NCBI
3	Schwartz L, Supuran CT and Alfarouk KO: The Warburg effect and the hallmarks of cancer. Anticancer Agents Med Chem. 17:164–170. 2017. View Article : Google Scholar : PubMed/NCBI
4	Ngo DC, Ververis K, Tortorella SM and Karagiannis TC: Introduction to the molecular basis of cancer metabolism and the Warburg effect. Mol Biol Rep. 42:819–823. 2015. View Article : Google Scholar : PubMed/NCBI
5	Allen AE and Locasale JW: Glucose metabolism in cancer: The saga of pyruvate kinase continues. Cancer Cell. 33:337–339. 2018. View Article : Google Scholar : PubMed/NCBI
6	Israelsen WJ and Vander Heiden MG: Pyruvate kinase: Function, regulation and role in cancer. Semin Cell Dev Biol. 43:43–51. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lu J, Chen M, Gao S, Yuan J, Zhu Z and Zou X: LY294002 inhibits the Warburg effect in gastric cancer cells by downregulating pyruvate kinase M2. Oncol Lett. 15:4358–4364. 2018.PubMed/NCBI
8	Li J, Cheng D, Zhu M, Yu H, Pan Z, Liu L, Geng Q, Pan H, Yan M and Yao M: OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer. Theranostics. 9:179–195. 2019. View Article : Google Scholar : PubMed/NCBI
9	Fu QF, Liu Y, Fan Y, Hua SN, Qu HY, Dong SW, Li RL, Zhao MY, Zhen Y, Yu XL, et al: Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway. J Hematol Oncol. 8:222015. View Article : Google Scholar : PubMed/NCBI
10	Zhao W, Li W, Dai W, Huang N and Qiu J: LINK-A promotes cell proliferation through the regulation of aerobic glycolysis in non-small-cell lung cancer. Onco Targets Ther. 11:6071–6080. 2018. View Article : Google Scholar : PubMed/NCBI
11	Chen H, Zhang M, Zhang W, Li Y, Zhu J, Zhang X, Zhao L, Zhu S and Chen B: Downregulation of BarH-like homeobox 2 promotes cell proliferation, migration and aerobic glycolysis through Wnt/β-catenin signaling, and predicts a poor prognosis in non-small cell lung carcinoma. Thorac Cancer. 9:390–399. 2018. View Article : Google Scholar : PubMed/NCBI
12	Hu T and Lu YR: BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer. Cancer Cell Int. 15:362015. View Article : Google Scholar : PubMed/NCBI
13	Li H, Zheng L, Jiang A, Mo Y and Gong Q: Identification of the biological affection of long noncoding RNA BC200 in Alzheimer's disease. Neuroreport. 29:1061–1067. 2018. View Article : Google Scholar : PubMed/NCBI
14	Booy EP, McRae EK, Koul A, Lin F and McKenna SA: The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol Cancer. 16:1092017. View Article : Google Scholar : PubMed/NCBI
15	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th Edition of the AJCC Cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
16	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
17	Lim SO, Li CW, Xia W, Lee HH, Chang SS, Shen J, Hsu JL, Raftery D, Djukovic D, Gu H, et al: EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape. Cancer Res. 76:1284–1296. 2016. View Article : Google Scholar : PubMed/NCBI
18	Kong XZ, Hu SS, Sun Z, Zuo LH, Kang J, Zhu ZF, Tian X and Zhang XJ: Regulation of aerobic glycolysis by long non-coding RNAs in cancer. Biochem Biophys Res Commun. 479:28–32. 2016. View Article : Google Scholar : PubMed/NCBI
19	Goncalves MD and Cantley LC: A glycolysis outsider steps into the cancer spotlight. Cell Metab. 28:3–4. 2018. View Article : Google Scholar : PubMed/NCBI
20	Chen R, Zhu S, Fan XG, Wang H, Lotze MT, Zeh HJ III, Billiar TR, Kang R and Tang D: High mobility group protein B1 controls liver cancer initiation through yes-associated protein-dependent aerobic glycolysis. Hepatology. 67:1823–1841. 2018. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Lu JH, Wu QN, Jin Y, Wang DS, Chen YX, Liu J, Luo XJ, Meng Q, Pu HY, et al: LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol Cancer. 18:1742019. View Article : Google Scholar : PubMed/NCBI
22	Li T, Sun X and Jiang X: UCA1 involved in the metformin-regulated bladder cancer cell proliferation and glycolysis. Tumour Biol. 39:10104283177108232017. View Article : Google Scholar : PubMed/NCBI
23	Zhang P, Cao L, Fan P, Mei Y and Wu M: LncRNA-MIF, a c-Myc-activated long non-coding RNA, suppresses glycolysis by promoting Fbxw7-mediated c-Myc degradation. EMBO Rep. 17:1204–1220. 2016. View Article : Google Scholar : PubMed/NCBI
24	Song J, Wu X, Liu F, Li M, Sun Y, Wang Y, Wang C, Zhu K, Jia X, Wang B and Ma X: Long non-coding RNA PVT1 promotes glycolysis and tumor progression by regulating miR-497/HK2 axis in osteosarcoma. Biochem Biophys Res Commun. 490:217–224. 2017. View Article : Google Scholar : PubMed/NCBI
25	Peng J, Hou F, Feng J, Xu SX and Men XY: Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo. Oncol Lett. 15:5809–5818. 2018.PubMed/NCBI
26	Gu L, Lu L, Zhou D and Liu Z: Long noncoding RNA BCYRN1 promotes the proliferation of colorectal cancer cells via Up-regulating NPR3 expression. Cell Physiol Biochem. 48:2337–2349. 2018. View Article : Google Scholar : PubMed/NCBI
27	Ren H, Yang X, Yang Y, Zhang X, Zhao R, Wei R, Zhang X and Zhang Y: Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma. Oncotarget. 9:4851–4861. 2017.PubMed/NCBI
28	Zhang XY, Tang XY, Ma LJ, Guo YL, Li XS, Zhao LM, Tian CJ, Cheng DJ, Chen ZC and Zhang LX: Schisandrin B down-regulated lncRNA BCYRN1 expression of airway smooth muscle cells by improving miR-150 expression to inhibit the proliferation and migration of ASMC in asthmatic rats. Cell Prolif. 50:e123822017. View Article : Google Scholar
29	Jin L, Li Y, Liu J, Yang S, Gui Y, Mao X, Nie G and Lai Y: Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Mol Med Rep. 13:5386–5392. 2016. View Article : Google Scholar : PubMed/NCBI
30	Wang Y, Zheng X, Zhang Z, Zhou J, Zhao G, Yang J, Xia L, Wang R, Cai X, Hu H, et al: MicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancer. PLoS One. 7:e416932012. View Article : Google Scholar : PubMed/NCBI
31	Wang F, Ma YL, Zhang P, Shen TY, Shi CZ, Yang YZ, Moyer MP, Zhang HZ, Chen HQ, Liang Y and Qin HL: SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol. 229:12–24. 2013. View Article : Google Scholar : PubMed/NCBI
32	Zhao L, Liu L, Dong Z and Xiong J: miR-149 suppresses human non-small cell lung cancer growth and metastasis by inhibiting the FOXM1/cyclin D1/MMP2 axis. Oncol Rep. 38:3522–3530. 2017.PubMed/NCBI
33	Qian B, Zhao L, Wang X, Xu J, Teng F, Gao L and Shen R: RETRACTED: miR-149 regulates the proliferation and apoptosis of cervical cancer cells by targeting GIT1. Biomed Pharmacother. 105:1106–1116. 2018. View Article : Google Scholar : PubMed/NCBI
34	Dayton TL, Jacks T and Vander Heiden MG: PKM2, cancer metabolism, and the road ahead. EMBO Rep. 17:1721–1730. 2016. View Article : Google Scholar : PubMed/NCBI
35	Dong G, Mao Q, Xia W, Xu Y, Wang J, Xu L and Jiang F: PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncol Lett. 11:1980–1986. 2016. View Article : Google Scholar : PubMed/NCBI
36	Papadaki C, Sfakianaki M, Lagoudaki E, Giagkas G, Ioannidis G, Trypaki M, Tsakalaki E, Voutsina A, Koutsopoulos A, Mavroudis D, et al: PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer. Br J Cancer. 111:1757–1764. 2014. View Article : Google Scholar : PubMed/NCBI
37	He J, Xie G, Tong J, Peng Y, Huang H, Li J, Wang N and Liang H: Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to 5-FU through the inhibition of PKM2 in vitro and in vivo. Cell Biochem Biophys. 70:1343–1350. 2014. View Article : Google Scholar : PubMed/NCBI
38	Wang HJ, Hsieh YJ, Cheng WC, Lin CP, Lin YS, Yang SF, Chen CC, Izumiya Y, Yu JS, Kung HJ and Wang WC: JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci USA. 111:279–284. 2014. View Article : Google Scholar : PubMed/NCBI
39	Luan W, Wang Y, Chen X, Shi Y, Wang J, Zhang J, Qian J, Li R, Tao T, Wei W, et al: PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop. Oncotarget. 6:13006–13018. 2015. View Article : Google Scholar : PubMed/NCBI