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Published on: May 30, 2025
Long noncoding RNA FER1L4 suppresses cancer cell growth by acting as a competing endogenous RNA and regulating PTEN
Tian Xia1, Shengcan Chen1, Zhen Jiang1
1Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, 315211, China.
Abstract:
Aberrantly expressed long noncoding RNAs (lncRNAs) are associated with various cancers. However, the roles of lncRNAs in the pathogenesis of most cancers are unclear. Here, we report that the lncRNA FER1L4 (fer-1-like family member 4, pseudogene) acts as a competing endogenous RNA (ceRNA) to regulate the expression of PTEN (a well-known tumor suppressor gene) by taking up miR-106a-5p in gastric cancer. We observed that FER1L4 was downregulated in gastric cancer and that its level corresponded with that of PTEN mRNA. Both FER1L4 and PTEN mRNA were targets of miR-106a-5p. Further experiments demonstrated that FER1L4 downregulation liberates miR-106a-5p and decreases the abundances of PTEN mRNA and protein. More importantly, FER1L4 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that one mechanism by which lncRNAs function in in tumorigenesis is as ceRNAs for tumor suppressor mRNAs.
Insights
The long noncoding RNA FER1L4 acts as a tumor suppressor in gastric cancer by regulating PTEN. Its downregulation releases miR-106a-5p, promoting cancer cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant expression of long noncoding RNAs (lncRNAs) is linked to various cancers, but their specific roles in pathogenesis remain largely unknown.
- Gastric cancer is a significant global health concern, necessitating a deeper understanding of its molecular underpinnings.
Purpose of the Study:
- To investigate the role of the long noncoding RNA FER1L4 in gastric cancer.
- To elucidate the molecular mechanism by which FER1L4 influences gastric cancer progression, specifically its interaction with microRNA-106a-5p and the tumor suppressor gene PTEN.
Main Methods:
- Quantitative real-time PCR to measure FER1L4 and PTEN mRNA levels in gastric cancer tissues.
- Bioinformatic analysis and luciferase reporter assays to confirm the interaction between FER1L4, miR-106a-5p, and PTEN.
- Cell cycle analysis to assess the impact of FER1L4 on cell proliferation.
Main Results:
- FER1L4 was found to be downregulated in gastric cancer tissues, with its expression correlating positively with PTEN mRNA levels.
- FER1L4 functions as a competing endogenous RNA (ceRNA) by sponging miR-106a-5p, thereby increasing PTEN expression.
- Downregulation of FER1L4 led to increased cell proliferation by promoting the G0/G1 to S phase transition, indicating a tumor-suppressive role.
Conclusions:
- The lncRNA FER1L4 acts as a ceRNA regulating PTEN expression via miR-106a-5p in gastric cancer.
- FER1L4 downregulation contributes to gastric tumorigenesis by inhibiting PTEN and promoting cell proliferation.
- lncRNAs can function as ceRNAs for tumor suppressor mRNAs, representing a potential therapeutic target in cancer.
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