Skip to main content
SpringerLink
Log in

CTBP1-AS2 promoted non-small cell lung cancer progression via sponging the miR-623/MMP3 axis

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Mounting evidence indicates that lncRNAs (long noncoding RNAs) are involved in the initiation and development of tumors, including non-small cell lung cancer (NSCLC). However, the involvement of C-terminal binding protein-antisense RNA 2 (CTBP1-AS2) in NSCLC remains to be studied. RT-qPCR was carried out to detect CTBP1-AS2 and miR-623 expression in NSCLC cells and tissues. CCK-8 and flow cytometry were performed to measure cell proliferation and cell cycle progression. Luciferase reporter analysis was performed to study the potential target of CTBP1-AS2. We found that CTBP1-AS2 expression was upregulated in NSCLC cells (SPC-A1, A549, H23, and H1299) compared to 16HBE cells. We demonstrated that the CTBP1-AS2 level was higher in NSCLC specimens than in paired non-tumor specimens. Elevated expression of CTBP1-AS2 increased cell growth and induced cell cycle progression and epithelial–mesenchymal transition (EMT). We also found that ectopic expression of CTBP1-AS2 inhibited miR-623 expression. MMP3 was a direct target of miR-623, and luciferase reporter assays suggested that miR-623 overexpression suppressed the luciferase expression driven by the MMP3 wild-type reporter but not the mutant reporter. Overexpression of miR-623 suppressed MMP3 expression in A549 cells, and overexpression of CTBP1-AS2 increased MMP3 expression in A549 cells. Moreover, the miR-623 level was lower in NSCLC specimens than in paired non-tumor specimens, and CTBP1-AS2 expression was negatively correlated with miR-623 expression in NSCLC samples. Furthermore, overexpression of CTBP1-AS2 enhanced cell growth, cell cycle progression, and EMT progression by modulating MMP3 expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

Research data are not shared.

References

  • Akagi I, Okayama H, Schetter AJ, Robles AI, Kohno T, Bowman ED, Kazandjian D, Welsh JA, Oue N, Saito M, Miyashita M, Uchida E, Takizawa T, Takenoshita S, Skaug V, Mollerup S, Haugen A, Yokota J, Harris CC (2013) Combination of protein coding and noncoding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma. Cancer Res 73:3821–3832

    Article  CAS  Google Scholar 

  • Brzóska K, Bartłomiejczyk T, Sochanowicz B, Cymerman M, Grudny J, Kołakowski J, Kruszewski M, Śliwiński P, Roszkowski-Śliż K, Kapka-Skrzypczak L (2018)Carcinogenesis-related changes in iron metabolism in chronic obstructive pulmonary disease subjects with lung cancer. Oncology letters 16:6831–6837

    Google Scholar 

  • Chung C, Yang J, He J, Yang X, Hubbard R, Ji D (2021) An investigation into the impact of variations of ambient air pollution and meteorological factors on lung cancer mortality in Yangtze River Delta. The Science of the total environment 779:146427

    Article  CAS  Google Scholar 

  • Cui ZH, Luo ZY, Lin ZM, Shi LH, Hong YR, Yan C (2019) Long non-coding RNA TTN-AS1 facilitates tumorigenesis of papillary thyroid cancer through modulating the miR-153-3p/ZNRF2 axis. Journal of Gene Medicine 21:e3083

    Article  CAS  Google Scholar 

  • Dong Z, Zhong Z, Yang L, Wang S, Gong Z (2014)MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer cells by regulating the drug transporter ABCB9. Cancer letters 343:249–257

    Article  CAS  Google Scholar 

  • Gong J, Xu X, Zhang X, Zhou Y (2020) Circular RNA-9119 suppresses in ovarian cancer cell viability via targeting the microRNA-21-5p-PTEN-Akt pathway. Aging 12:14314–14328

    Article  CAS  Google Scholar 

  • Gu C, Luo Y, Zhang S, Xu J, Zhang J, Ju H, Liu J, Zhang L, Zhang Y, Wu L, Xie E, Xu T, Pan S (2020) MAb NJ001 inhibits lung adenocarcinoma invasiveness by directly regulating TIMP-3 promoter activity via FOXP1 binding sites. Thoracic cancer 11:2630–2638

    Article  CAS  Google Scholar 

  • Guo W, Yu Q, Zhang M, Li F, Liu Y, Jiang W, Jiang H, Li H (2019a) Long intergenic non-protein coding RNA 511 promotes the progression of osteosarcoma cells through sponging microRNA 618 to upregulate the expression of maelstrom. Aging 11:5351–5367

    Article  CAS  Google Scholar 

  • Guo XC, Li L, Gao ZH, Zhou HW, Li J, Wang QQ (2019b) The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1. Aging 11:1333–1341

    Article  CAS  Google Scholar 

  • Han YY, Wu N, Jiang MZ, Chu Y, Wang ZY, Liu H, Cao JY, Liu HM, Xu B, Xie X (2019) Long non-coding RNA MYOSLID functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-29c-3p in gastric cancer. Cell Prolif 52:e12678

    Article  Google Scholar 

  • Hu R, Zhu ZM (2019): ELK1-activated GPC3-AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells. J Gene Med 21. 21(8):e3099.

  • Hu XF, Duan L, Liu HC, Zhang L (2019a) Long noncoding RNA LINC01296 induces non-small cell lung cancer growth and progression through sponging miR-5095. American journal of translational research 11:895–903

    CAS  Google Scholar 

  • Hu XH, Tan ZX, Yang YJ, Yang PH (2019b) Long non-coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/-catenin signaling pathway. Journal of Gene Medicine 21:e3085

    Article  CAS  Google Scholar 

  • Jia B, Xie T, Qiu X, Sun X, Chen J, Huang Z, Zheng X, Wang Z, Zhao J (2019) Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2. Aging 11:4990–5007

    Article  CAS  Google Scholar 

  • Jiang Q, Xing W, Cheng J, Yu Y (2020) Knockdown of lncRNA XIST suppresses cell tumorigenicity in human non-small cell lung cancer by regulating miR-142-5p/PAX6 Axis. OncoTargets and therapy 13:4919–4929

    Article  CAS  Google Scholar 

  • Li CL, Tan FB, Pei Q, Zhou ZY, Zhou Y, Zhang LQ, Wang D, Pei HP (2019a)Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis. Cell proliferation 52:e12632

    Google Scholar 

  • Li M, Chen Y, Zhu JC, Gao Z, Wang T, Zhou PL (2019b) Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer. Am J Transl Res 11:4303

    CAS  Google Scholar 

  • Li Z, Li XY, Chen X, Li SG, Ho IHT, Liu XD, Chan MTV, Wu WKK (2019c) Emerging roles of long non-coding RNAs in neuropathic pain. Cell Prolif 52:e12528

    Article  Google Scholar 

  • Li Z, Li X, Shen J, Zhang L, Chan MTV, Wu WKK (2020) Emerging roles of non-coding RNAs in scoliosis. Cell Prolif 53:e12736

    Google Scholar 

  • Liao K, Yong C, Hua K (2018) SB431542 inhibited cigarette smoke extract induced invasiveness of A549 cells via the TGF-β1/Smad2/MMP3 pathway. Oncology letters 15:9681–9686

    Google Scholar 

  • Liu X, Ma BD, Liu S, Liu J, Ma BX (2019) Long noncoding RNA LINC00341 promotes the vascular smooth muscle cells proliferation and migration via miR-214/FOXO4 feedback loop. Am J Transl Res 11:1835

    CAS  Google Scholar 

  • Liu X, Huang S, Guan Y, Zhang Q (2020a) Long noncoding RNA OSER1-AS1 promotes the malignant properties of non-small cell lung cancer by sponging microRNA-433-3p and thereby increasing Smad2 expression. Oncol Rep 44:599–610

    Article  CAS  Google Scholar 

  • Liu Y, Li L, Shang P, Song X (2020b): LncRNA MEG8 promotes tumor progression of non-small cell lung cancer via regulating miR-107/CDK6 axis. Anticancer Drugs. 31(10):1065-1073.

  • Okusha Y, Eguchi T, Tran M, Sogawa C, Yoshida K, Itagaki M, Taha E, Ono K, Aoyama E, Okamura H, Kozaki K, Calderwood S, Takigawa M, Okamoto K (2020): CCN2/CTGF Extracellular Vesicles enriched with moonlighting metalloproteinase are highly transmissive, pro-tumorigenic, and trans-activates cellular communication network factor: CRISPR against Cancer. Cancers 12(4):881.

  • Onyeuwaoma N, Okoh D, Okere B (2021) A neural network-based method for modeling PM 2.5 measurements obtained from the surface particulate matter network. Environ Monit Assess 193:261

    Article  CAS  Google Scholar 

  • Pan R, Zhou H (2020) Exosomal Transfer of lncRNA H19 promotes erlotinib resistance in non-small cell lung cancer via miR-615-3p/ATG7 Axis. Cancer management and research 12:4283–4297

    Article  CAS  Google Scholar 

  • Refai NS, Louka ML, Halim HY, Montasser I (2019) Long non-coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: clinical significance. Journal of Gene Medicine 21:e3112

    Article  CAS  Google Scholar 

  • Schliekelman MJ, Taguchi A, Zhu J, Dai X, Rodriguez J, Celiktas M, Zhang Q, Chin A, Wong CH, Wang H, McFerrin L, Selamat SA, Yang C, Kroh EM, Garg KS, Behrens C, Gazdar AF, Laird-Offringa IA, Tewari M et al (2015) Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival. Cancer research 75:1789–1800

    Article  CAS  Google Scholar 

  • Shamsollahi H, Jahanbin B, Rafieian S, Yunesian M (2021) Particulates induced lung inflammation and its consequences in the development of restrictive and obstructive lung diseases: a systematic review. Environmental science and pollution research international 28:25035–25050

    Article  CAS  Google Scholar 

  • She KL, Yan H, Huang J, Zhou HP, He JX (2018): miR-193b availability is antagonized by LncRNA-SNHG7 for FAIM2-induced tumour progression in non-small cell lung cancer. Cell Prolif 51(1):e12406.

  • Song Q, Xu Y, Yang C, Chen Z, Jia C, Chen J, Zhang Y, Lai P, Fan X, Zhou X, Lin J, Li M, Ma W, Luo S, Bai X (2014)miR-483-5p promotes invasion and metastasis of lung adenocarcinoma by targeting RhoGDI1 and ALCAM. Cancer Res 74:3031–3042

    Article  CAS  Google Scholar 

  • Sun Z, He CZ, Xiao M, Wei BB, Zhu YZ, Zhang GX, Zhou HY, Yuan J, Hu XJ, Yi YL (2019) LncRNA FOXC2 antisense transcript accelerates non-small-cell lung cancer tumorigenesis via silencing p15. American journal of translational research 11:4552

    CAS  Google Scholar 

  • Tsai H, Su H, Huang C, Fong Y, Hsu C, Tang C (2014) CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d. Oncotarget 5:3800–3812

    Article  Google Scholar 

  • Wang M, Zhao H (2020): LncRNA CTBP1-AS2 promotes cell proliferation in hepatocellular carcinoma by regulating miR-623/cyclin D1 axis. Cancer Biother Radiopharm. 35(10):765-770.

  • Wang Y, Xu L, Jiang L (2015) miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5. Biochemical and biophysical research communications 458:714–719

    Article  CAS  Google Scholar 

  • Wang HX, Kang LJ, Qin X, Xu J, Fei JW (2020) LINC00460 promotes proliferation and inhibits apoptosis of non-small cell lung cancer cells through targeted regulation of miR-539. European review for medical and pharmacological sciences 24:6752–6758

    Google Scholar 

  • Xie N, Fei XQ, Liu SL, Liao J, Li YJ (2019) LncRNA LOXL1-AS1 promotes invasion and proliferation of non-small-cell lung cancer through targeting miR-324-3p. American journal of translational research 11:6403–6412

    CAS  Google Scholar 

  • Ye P, Lv XY, Aizemaiti R, Cheng J, Xia PH, Di M (2020): H3K27ac-activated LINC00519 promotes lung squamous cell carcinoma progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis. Cell Prolif 53(5):e12797.

  • Yuan Y, Wang Q, Ma SL, Xu LQ, Liu MY, Han B, Du N, Sun XL, Yin XL, Cao FF (2019) lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/beta-catenin signaling pathway. American journal of translational research 11:7104–7114

    CAS  Google Scholar 

  • Zeng Q, Dai Y, Duan C, Zeng R, Zeng Q, Wei C (2020) Long noncoding RNA POU3F3 enhances cancer cell proliferation, migration and invasion in non-small cell lung cancer (adenocarcinoma) by downregulating microRNA-30d-5p. BMC pulmonary medicine 20:185

    Article  CAS  Google Scholar 

  • Zhang C, Su C, Song Q, Dong F, Yu S, Huo J (2018) LncRNA PICART1 suppressed non-small cell lung cancer cells proliferation and invasion by targeting AKT1 signaling pathway. American J Transl Res 10:4193–4201

    CAS  Google Scholar 

  • Zhang LN, Cao YF, Kou XN, Che L, Zhou XN, Chen G, Zhao J (2019a) Long non-coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis. J Gene Med 21:e3074

    Article  CAS  Google Scholar 

  • Zhang M, Song YH, Yu LJ (2019b) LncRNA PTCSC3 suppressed cervical carcinoma cell invasion and proliferation via regulating miR-574-5p. American journal of translational research 11:7186–7194

    CAS  Google Scholar 

  • Zhang XD, Gong J, Lu JG, Chen J, Zhou Y, Li T, Ding LC (2019c) Long noncoding RNA LINC00337 accelerates the non-small-cell lung cancer progression through inhibiting TIMP2 by recruiting DNMT1. Am J Transl Res 11:6075

    CAS  Google Scholar 

  • Zhang Z, Nong L, Chen ML, Gu XL, Zhao WW, Liu MH, Cheng WW (2020): LncRNA ELF3-AS1 Promotes nonsmall cell lung cancer cell invasion and migration by downregulating miR-212. Cancer Biother. Radiopharm. Online ahead of print.

  • Zhao Z, Jin J, Zhang A, Zhang L, Wang X, Sun J, Chen Z (2015) MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma. Journal of cellular biochemistry 116:458–466

    Article  CAS  Google Scholar 

  • Zhao K, Zhang Y, Yuan H, Zhao M, Zhao D (2019) Long noncoding RNA LINC00958 accelerates the proliferation and matrix degradation of the nucleus pulposus by regulating miR-203/SMAD3. Aging 11:10814–10825

    Article  CAS  Google Scholar 

  • Zhao L, Zhang X, Guo H, Liu M, Wang L (2020a)LOXL1-AS1 contributes to non-small cell lung cancer progression by regulating miR-3128/RHOXF2 Axis. OncoTargets and therapy 13:6063–6071

    Article  CAS  Google Scholar 

  • Zhao W, Chen T, Zhao Y (2020b) Upregulated lncRNA CASC9 Contributes to progression of non-small cell lung cancer through inhibition of miR-335-3p and activation S100A14 expression. OncoTargets and therapy 13:6027–6036

    Article  CAS  Google Scholar 

  • Zheng Z, Li X, You H, Zheng X, Ruan X (2020): LncRNA SOCS2-AS1 inhibits progression and metastasis of colorectal cancer through stabilizing SOCS2 and sponging miR-1264. Aging 12(11):10517-10526

    Article  CAS  Google Scholar 

  • Zhou XY, Xu XH, Gao C, Cui YS (2019) XIST promote the proliferation and migration of non-small cell lung cancer cells via sponging miR-16 and regulating CDK8 expression. American journal of translational research 11:6196–6206

    CAS  Google Scholar 

  • Zhu H, Kong L (2019) LncRNA CRNDE regulates trophoblast cell proliferation, invasion, and migration via modulating miR-1277. American journal of translational research 11:5905–5918

    CAS  Google Scholar 

  • Zhu DL, Zhang X, Lin Y, Liang SJ, Song ZW, Dong CY (2019) MT1JP inhibits tumorigenesis and enhances cisplatin sensitivity of breast cancer cells through competitively binding to miR-24-3p. American journal of translational research 11:245–256

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Occupational Disease, Daqing People’s Hospital, Daqing, 163316, Heilongjiang, China

    Guanying Yang & Chunjie Zhang

Authors
  1. Guanying Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunjie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Guangying Yang and Chunjie Zhang conducted experiments, collected and analyzed data, and wrote and revised this manuscript.

Corresponding author

Correspondence to Chunjie Zhang.

Ethics declarations

Ethics approval

All patients signed informed consent, and our protocol was approved with Ethics Clinical Committee of Daqing People’s Hospital.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, G., Zhang, C. CTBP1-AS2 promoted non-small cell lung cancer progression via sponging the miR-623/MMP3 axis. Environ Sci Pollut Res 29, 38385–38394 (2022). https://doi.org/10.1007/s11356-021-15921-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-15921-z

Keywords

Search

Navigation