Abstract
Background
Colorectal cancer (CRC) is one of the most prevalent malignant cancers worldwide. High recurrence and poor prognosis are caused by chemotherapy resistance and stem-cell-like characteristics in CRC patients.
Objective
To research the underlying molecular pathways and create novel treatment approaches.
Results
We found that PTPRG-AS1 were increased in CRC tumor tissue and oxaliplatin-resistant CRC cells. Knockdown of PTPRG-AS1 can reduce the half-maximal inhibitory concentration (IC50) values and proliferating cells while increase number of apoptotic cells and reduced stem cell-like properties in oxaliplatin-resistant CRC cells. Furthermore, the study of mechanism verified that PTPRG-AS1 could increase STAT3 expression through miR-665 to promote tumor progression of CRC.
Conclusion
In this study, PTPRG-AS1 maintains stemness features and promotes oxaliplatin resistance in CRC through modulating miR-665/STAT3.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig5_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13273-022-00314-1/MediaObjects/13273_2022_314_Fig6_HTML.png)
Similar content being viewed by others
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
References
André T et al (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27:3109–3116
Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152:1298–1307
Chen G et al (2021) LncRNA PTPRG-AS1 promotes the metastasis of hepatocellular carcinoma by enhancing YWHAG. J Oncol 2021:3624306
Connell LC, Mota JM, Braghiroli MI, Hoff PM (2017) The rising incidence of younger patients with colorectal cancer: questions about screening, biology, and treatment. Curr Treat Options Oncol 18:23
Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284
Dong M et al (2021) CircMYBL2 regulates the resistance of cervical cancer cells to paclitaxel via miR-665-dependent regulation of EGFR. Drug Dev Res 82:1193–1205
Fan C et al (2020) Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells. Cancer Cell Int 20:473
Linnekamp JF, Wang X, Medema JP, Vermeulen L (2015) Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes. Can Res 75:245–249
Liu T et al (2019) Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer. Mol Cancer 18:43
Ma Q et al (2020) Long noncoding RNA PTPRG antisense RNA 1 reduces radiosensitivity of nonsmall cell lung cancer cells via regulating MiR-200c-3p/TCF4. Technol Cancer Res Treat 19:1533033820942615
Mani SA et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715
Ouyang S et al (2019) LncRNA BCAR4, targeting to miR-665/STAT3 signaling, maintains cancer stem cells stemness and promotes tumorigenicity in colorectal cancer. Cancer Cell Int 19:72
Park SY et al (2019) The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance. J Exp Clin Cancer Res 38:399
Qian XL et al (2021) MiR-454-3p promotes oxaliplatin resistance by targeting PTEN in colorectal cancer. Front Oncol 11:638537
Shi J et al (2020) Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression. Ovarian Res 13:127
Sun J et al (2021) lncRNA TUG1 facilitates colorectal cancer Stem cell characteristics and chemoresistance by enhancing GATA6 protein stability. Stem Cells Int 2021:1075481
Todaro M et al (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402
Wang LX et al (2019a) Integrative analysis of long noncoding RNA (lncRNA), microRNA (miRNA) and mRNA expression and construction of a competing endogenous RNA (ceRNA) network in metastatic melanoma. Med Sci Monitor 25:2896–2907
Wang M et al (2019b) Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ 26:2329–2343
Wang H et al (2020) MicroRNA-181d-5p-containing exosomes derived from CAFs promote EMT by regulating CDX2/HOXA5 in breast cancer. Mol Ther Nucl Acids 19:654–667
Wang Y, Cheng Z, Xu J, Lai M, Liu L, Zuo M, Dang L (2021) Fat mass and obesity-associated protein (FTO) mediates signal transducer and activator of transcription 3 (STAT3)-drived resistance of breast cancer to doxorubicin. Bioengineered 12(1):1874–1889
Wu CP, Ambudkar SV (2014) The pharmacological impact of ATP-binding cassette drug transporters on vemurafenib-based therapy. Acta Pharmaceutica Sinica. B 4:105–111
Wu ZX et al (2019) Tepotinib reverses ABCB1-mediated multidrug resistance in cancer cells. Biochem Pharmacol 166:120–127
Wu K et al (2022) LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis. J Gastroenterol Hepatol 37:507–517
Xue Y et al (2021) Long noncoding RNAs PTPRG antisense RNA 1 targets cyclin D1 to facilitate cell proliferation in lung adenocarcinoma. Cancer Biother Radiopharmaceut. https://doi.org/10.1089/cbr.2021.0168
Yang AD et al (2006) Chronic oxaliplatin resistance induces epithelial-to-mesenchymal transition in colorectal cancer cell lines. Clin Cancer Res 12:4147–4153
Yi L et al (2019) Long noncoding RNA PTPRG-AS1 acts as a microRNA-194-3p sponge to regulate radiosensitivity and metastasis of nasopharyngeal carcinoma cells via PRC1. J Cell Physiol 234:19088–19102
Zeng J, Ma YX, Liu ZH, Zeng YL (2019) LncRNA SNHG7 contributes to cell proliferation, invasion and prognosis of cervical cancer. Eur Rev Med Pharmacol Sci 23:9277–9285
Zhang Y et al (2019) circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637. EBioMedicine 48:277–288
Funding
This work was supported by the Basic Research Program of Guizhou Province (Grant No. ZK [2021] General 453) and Science and Technology Fund of Guizhou Provincial Health Construction Commission (Grant No. gzwjkj2020-1-097).
Author information
Authors and Affiliations
Contributions
XL and CF designed the study, completed the experiment and supervised the data collection, LH analyzed the data, interpreted the data, MX and SO prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
Author Chendong Fu declares that he/she has no conflict of interest; author **anting Li declares that he/she has no conflict of interest; author Lang Han declares that he/she has no conflict of interest; author Ming **e declares that he/she has no conflict of interest; author Shurui Ouyang declares that he/she has no conflict of interest.
Ethical approval
Ethical approval was obtained from the Ethics Committee of Affiliated Hospital of Zunyi Medical University.
Informed consent
Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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.
About this article
Cite this article
Fu, C., Li, X., Han, L. et al. LncRNA PTPRG-AS1 maintains stem-cell-like features and promotes oxaliplatin resistance in colorectal cancer via regulating the miR-665 and STAT3 axis. Mol. Cell. Toxicol. 20, 35–45 (2024). https://doi.org/10.1007/s13273-022-00314-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13273-022-00314-1