Skip to main content
SpringerLink
Log in

LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and frequent cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) play regulatory roles and serve as biomarkers of multiple cancers, including ESCC. Our previous studies have confirmed that lncRNA Kinectin 1 antisense RNA 1 (KTN1-AS1) is highly expressed in ESCC and exerts oncogene function through RBBP4/HDAC1 complex.

Objective

Our present study focused on exploring a novel molecular mechanism of KTN1-AS1 in ESCC.

Methods

In this study, qRT-PCR assay, Western blot assay, Luciferase reporter assay, and RNA immunoprecipitation assay were conducted.

Results

We found that KTN1-AS1 could bind to miR-885-5p in ESCC cells, and miR-885-5p was low expressed in ESCC. Overexpression of miR-885-5p inhibited esophageal cancer cells proliferation and invasion in vitro. Mechanistic analysis demonstrated that miR-885-5p specifically targeted striatin 3 (STRN3), and KTN1-AS1/miR-885-5p promoted the EMT process by Hippo pathway in STRN3/YAP1 dependent manner.

Conclusion

To sum up, KTN1-AS1 facilitates ESCC progression by acting as a ceRNA for miR-885-5p to regulate STRN3 expression and the Hippo pathway, and KTN1-AS1 maybe used as a promising therapeutic target for ESCC.

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

Similar content being viewed by others

Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Arnold M, Soerjomataram I, Ferlay J, Forman D (2015) Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64(3):381–387

    Article  PubMed  Google Scholar 

  • Bhan A, Soleimani M, Mandal SS (2017) Long noncoding RNA and cancer: a new paradigm. Cancer Res 77(15):3965–3981

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  PubMed  Google Scholar 

  • Chen MJ, Deng J, Chen C, Hu W, Yuan YC, Xia ZK (2019) LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis. Int J Biochem Cell Biol 113:27–36

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Lu J, Xu T, Yan Z, Guo Y, Dong Z, Guo W (2022) KTN1-AS1, a SOX2-mediated lncRNA, activates epithelial-mesenchymal transition process in esophageal squamous cell carcinoma. Sci Rep 12(1):20186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo F, Parker Kerrigan BC, Yang D, Hu L, Shmulevich I, Sood AK, Xue F, Zhang W (2014) Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions. J Hematol Oncol 7:19

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo K, Qian K, Shi Y, Sun T, Wang Z (2021) LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p. Cell Death Dis 12(12):1097

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo K, Fang L, Li M, Li A, Liu N (2023) Long Non-coding RNA KTN1-AS1 targets miR-505 to promote glioblastoma progression. Behav Neurol 2023:4190849

    Article  PubMed  PubMed Central  Google Scholar 

  • Herman AB, Tsitsipatis D, Gorospe M (2022) Integrated lncRNA function upon genomic and epigenomic regulation. Mol Cell 82(12):2252–2266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hu Y, Ma Y, Luo G, Liao W, Zhang S, Li G (2021) Effect of MiR-375 regulates YAP1 on the invasion, apoptosis, and epithelial–mesenchymal transition of cervical cancer HeLa cells. Evid Based Complement Alternat Med 2021:3088723

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang Y, Wu K, Cao W, Xu Q, Wang X, Qin X, Wang X, Li Y, Zhang J, Chen W (2020) Long noncoding RNA KTN1-AS1 promotes head and neck squamous cell carcinoma cell epithelial–mesenchymal transition by targeting miR-153-3p. Epigenomics 12(6):487–505

    Article  PubMed  CAS  Google Scholar 

  • Kong X, Duan Y, Sang Y, Li Y, Zhang H, Liang Y, Liu Y, Zhang N, Yang Q (2019) LncRNA-CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA-215. J Cell Physiol 234(6):9105–9117

    Article  PubMed  CAS  Google Scholar 

  • Li C, Zhao W, Pan X, Li X, Yan F, Liu S, Feng J, Lu J (2020) LncRNA KTN1-AS1 promotes the progression of non-small cell lung cancer via sponging of miR-130a-5p and activation of PDPK1. Oncogene 39(39):6157–6171

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Sun C, Tan Y, Zhang H, Li Y, Zou H (2021) ITGB1 enhances the radioresistance of human non-small cell lung cancer cells by modulating the DNA damage response and YAP1-induced epithelial–mesenchymal transition. Int J Biol Sci 17(2):635–650

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu C, Li X, Hao Y, Wang F, Cheng Z, Geng H, Geng D (2020) STAT1-induced upregulation of lncRNA KTN1-AS1 predicts poor prognosis and facilitates non-small cell lung cancer progression via miR-23b/DEPDC1 axis. Aging (Albany NY) 12(9):8680–8701

    Article  PubMed  CAS  Google Scholar 

  • Lv C, Yu H, Wang K, Chen C, Tang J, Han F, Mai M, Ye K, Lai M, Zhang H (2022) ENO2 promotes colorectal cancer metastasis by interacting with the LncRNA CYTOR and activating YAP1-induced EMT. Cells 11(15):2363

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mu Y, Tang Q, Feng H, Zhu L, Wang Y (2020) lncRNA KTN1-AS1 promotes glioma cell proliferation and invasion by negatively regulating miR-505-3p. Oncol Rep 44(6):2645–2655

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pastushenko I, Blanpain C (2019) EMT transition states during tumor progression and metastasis. Trends Cell Biol 29(3):212–226

    Article  PubMed  CAS  Google Scholar 

  • Qu Y, Zhang L, Wang J, Chen P, Jia Y, Wang C, Yang W, Wen Z, Song Q, Tan B, Cheng Y (2019) Yes-associated protein (YAP) predicts poor prognosis and regulates progression of esophageal squamous cell cancer through epithelial-mesenchymal transition. Exp Ther Med 18(4):2993–3001

    PubMed  PubMed Central  CAS  Google Scholar 

  • Su M, Qin B, Liu F, Chen Y, Zhang R (2018) miR-885-5p upregulation promotes colorectal cancer cell proliferation and migration by targeting suppressor of cytokine signaling. Oncol Lett 16(1):65–72

    PubMed  PubMed Central  Google Scholar 

  • Tang Y, Fang G, Guo F, Zhang H, Chen X, An L, Chen M, Zhou L, Wang W, Ye T, Zhou L, Nie P, Yu H, Lin M, Zhao Y, Lin X, Yuan Z, Jiao S, Zhou Z (2020) Selective inhibition of STRN3-containing PP2A phosphatase restores hippo tumor-suppressor activity in gastric cancer. Cancer Cell 38(1):115–128

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Zhao Y, Lu Q, Fei X, Lu C, Li C, Chen H (2020) MiR-34a-5p inhibits proliferation, migration, invasion and epithelial-mesenchymal transition in esophageal squamous cell carcinoma by targeting LEF1 and inactivation of the hippo-YAP1/TAZ signaling pathway. J Cancer 11(10):3072–3081

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, Imamura Y (2020) Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today 50(1):12–20

    Article  PubMed  Google Scholar 

  • Xie X, Wen Q, Yang X, Chen W, Liu Y, Liu W, Zhang T, Xu C, Shi K (2022) H3K27ac-activated lncRNA KTN1-AS1 aggravates tumor progression by miR-505-3p/ZNF326 axis in ovarian cancer. Ann Transl Med 10(10):599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu F, Zhang J (2017) Long non-coding RNA HOTAIR functions as miRNA sponge to promote the epithelial to mesenchymal transition in esophageal cancer. Biomed Pharmacother 90:888–896

    Article  PubMed  CAS  Google Scholar 

  • Yan H, Li H, Silva MA, Guan Y, Yang L, Zhu L, Zhang Z, Li G, Ren C (2019) LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer. J Exp Clin Cancer Res 38(1):356

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang H, Su H, Hu N, Wang C, Wang L, Giffen C, Goldstein AM, Lee MP, Taylor PR (2020) Integrated analysis of genome-wide miRNAs and targeted gene expression in esophageal squamous cell carcinoma (ESCC) and relation to prognosis. BMC Cancer 20(1):388

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yao P, Li Y, Shen W, Xu X, Zhu W, Yang X, Cao J, Xing C (2018) ANKHD1 silencing suppresses the proliferation, migration and invasion of CRC cells by inhibiting YAP1-induced activation of EMT. Am J Cancer Res 8(11):2311–2324

    PubMed  PubMed Central  CAS  Google Scholar 

  • Yu M, Chen Y, Li X, Yang R, Zhang L, Huangfu L, Zheng N, Zhao X, Lv L, Hong Y, Liang H, Shan H (2018) YAP1 contributes to NSCLC invasion and migration by promoting Slug transcription via the transcription co-factor TEAD. Cell Death Dis 9(5):464

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang ZB, Liu N (2021) Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating microRNA-23b-3p/high-mobility group box 2 axis. Aging (Albany NY) 13(16):20820–20835

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Yin J, Yang J, Shen W, Zhang C, Mou W, Luo J, Yan H, Sun P, Luo Y, Tian Y, Xiang R (2016) miR-885-5p suppresses hepatocellular carcinoma metastasis and inhibits Wnt/β-catenin signaling pathway. Oncotarget 7(46):75038–75051

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Wang L, Wang Y, Chen T, Liu R, Yang W, Liu Q, Tu K (2019) LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis. Biomed Pharmacother 109:1140–1147

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was supported by Grants from the Natural Science Foundation of Hebei Province (no. H2021206259 and H2022206598) and National Natural Science Foundation of China (no. 82203622).

Author information

Authors and Affiliations

  1. Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China

    Liying Chen

  2. Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, Hebei, 050011, China

    Juntao Lu, Xiaoxu Li, Xinhao Wang & Wei Guo

  3. Hebei Medical University, Shijiazhuang, Hebei, China

    Ruoyang Qiao

  4. Department of Human Anatomy, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, Hebei, 050017, China

    Qian Ren

Authors
  1. Liying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juntao Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoxu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinhao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruoyang Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qian Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by LC, JL, and XL. Data analysis was performed by XW and RQ. The first draft of the manuscript was written by LC and all authors commented on previous versions of the manuscript. Conception and revision of the manuscript were performed by WG and QR. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Guo or Qian Ren.

Ethics declarations

Conflict of interest

The authors declare they have no financial interests.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Forth Hospital of Hebei Medical University.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1113 KB)

Supplementary file2 (DOCX 18 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, L., Lu, J., Li, X. et al. LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis. Genes Genom 46, 241–252 (2024). https://doi.org/10.1007/s13258-023-01451-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-023-01451-0

Keywords

Search

Navigation