Abstract
Background
Chemotherapy is, next to surgery and radiotherapy, the mainstay regimen for the clinical management of gastric cancer. This therapy is, however, heavily compromised by the acquisition of resistance. Here, we aimed to clarify the potential involvement of long non-coding RNA SNGH3 in the acquisition of cisplatin resistance and stemness in gastric cancer.
Methods
Cell viability and proliferation were measured using Cell Counting Kit-8 and colony formation assays, respectively. Stem cell-like cell growth was evaluated using a mammosphere formation assay. RNA levels of SNHG2, OCT-4, SOX-2, CD44, miR-3619-5p and ARL2 were determined using qRT-PCR, whereas protein levels of OCT-4, SOX-2, CD44, ARL2, STAT3 and pSTAT3 were determined using Western blotting. Dual luciferase reporter assays were employed to interrogate regulatory interactions between STAT3, SNHG3, miR-3619-5p and ARL2, respectively. Direct binding of STAT3 to the SNHG3 promoter was investigated using a chromatin immunoprecipitation assay.
Results
We found that IL-6 triggered stem cell-like properties in cisplatin-treated gastric cancer cells and activated STAT3, which in turn transcriptionally regulated SNHG3 expression. SNHG3 expression up-regulation positively correlated with cisplatin resistance and stemness of gastric cancer cells, while SNHG3 down-regulation inhibited stem cell-like properties. In addition, we found that SNHG3 up-regulated ARL2 expression through sponging miR-3619-5p, which predominantly mediated the oncogenic properties of SNHG3 in this disease.
Conclusions
Our data indicate an involvement of aberrant SNHG3 over-expression in the acquisition of both cisplatin resistance and stemness of gastric cancer cells, and of the IL-6/STAT3/SNHG3/miR-3619-5p/ARL2 signaling cascade in the oncogenic properties of SNHG3.
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Data Availability
Not applicable.
Change history
01 February 2022
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s13402-022-00662-z
Abbreviations
- lncRNA:
-
Long non-coding RNA
- ChIP:
-
Chromatinimmunoprecipitation
- ATCC:
-
American Type CultureCollection
- CCK-8:
-
Cell Counting Kit-8
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Funding
This work was supported by Shanghai Anticancer Association “aoxiang” Project (SACA-AX201901).
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Bo Sun, Yang Han, Hong Cai, Hua Huang and Yi Xuan collected and assembled the data. Bo Sun and Yang Han performed the statistical analyses. Hong Cai and Yi Xuan conceived and designed the study and wrote the manuscript. All authors read and approved the final manuscript.
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The study was approved by the Institutional Ethics Committee of Fudan University Shanghai Cancer Center and performed in strict accordance to NIH guidelines.
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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s13402-022-00662-z
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Sun, B., Han, Y., Cai, H. et al. RETRACTED ARTICLE: Long non-coding RNA SNHG3, induced by IL-6/STAT3 transactivation, promotes stem cell-like properties of gastric cancer cells by regulating the miR-3619-5p/ARL2 axis. Cell Oncol. 44, 179–192 (2021). https://doi.org/10.1007/s13402-020-00560-2
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DOI: https://doi.org/10.1007/s13402-020-00560-2
Keywords
- gastric cancer
- SNHG3
- stem cell
- cisplatin resistance
- miR-3619-5p