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Published on: May 30, 2025
The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging
Zhaoliang Chen1, Hong Liu1, Huili Yang1
1Department of Oncology, Binzhou Central Hospital, Binzhou, Shandong.
Background:
Accumulating evidence indicates that the long noncoding RNA, TINCR, plays a critical role in cancer progression and metastasis. However, the overall biological role and mechanisms of TINCR that were involved in human gastric cancer (GC) progression remain largely unknown.
Methods:
TINCR expression was measured in 56 paired tumor and adjacent nontumor tissue samples by real-time polymerase chain reaction (PCR). Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays. The effects of TINCR and miR-375 on GC cell apoptosis and proliferation were studied by RNA interference approaches in vitro and in vivo. The correlation of TINCR and PDK1 was identified by real-time PCR and Western blot analysis.
Results:
Our results showed that miR-375 level decreased and TINCR level increased in tumor tissues. In addition, TINCR was a target of miR-375 and inhibited its expression in GC cells. Furthermore, the low expression of TINCR increased cell apoptosis and inhibited the proliferation of GC cells, while the downregulation of miR-375 reversed the function. In particular, TINCR could negatively regulate the miR-375 expression and increased the PDK1 expression in GC cells. Finally, tumor growth suppression was retarded with miR-375 downregulated in TINCR knockdown of GC cell xenografts.
Conclusion:
The long noncoding RNA TINCR functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in GC. The ceRNA regulatory network of TINCR/miR-375/PDK1 allows us to better understand the pathogenesis of GC and facilitate the development of long noncoding RNA (lncRNA)-directed diagnostics in GC.
Insights
The long noncoding RNA TINCR promotes gastric cancer by inhibiting miR-375, leading to increased PDK1 expression. Targeting this TINCR/miR-375/PDK1 pathway may offer new diagnostic and therapeutic strategies for gastric cancer.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNA TINCR is implicated in cancer progression and metastasis.
- The specific role and mechanisms of TINCR in human gastric cancer (GC) remain largely uncharacterized.
Purpose of the Study:
- To elucidate the biological role and molecular mechanisms of TINCR in gastric cancer progression.
- To investigate the regulatory network involving TINCR, miR-375, and PDK1 in GC.
Main Methods:
- Quantitative real-time PCR and Western blot analysis for TINCR and PDK1 expression.
- Bioinformatic analysis and luciferase assays to explore competing endogenous RNA (ceRNA) mechanisms.
- In vitro and in vivo RNA interference studies to assess the functional impact of TINCR and miR-375 on GC cells.
Main Results:
- TINCR expression was upregulated, while miR-375 was downregulated in GC tissues.
- TINCR acts as a sponge for miR-375, inhibiting its activity and leading to increased PDK1 expression.
- Reduced TINCR expression suppressed GC cell proliferation and induced apoptosis, effects reversed by miR-375 downregulation.
Conclusions:
- The TINCR/miR-375/PDK1 axis represents a novel ceRNA regulatory network in GC.
- This pathway provides a deeper understanding of GC pathogenesis and suggests potential lncRNA-directed diagnostic and therapeutic targets.
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