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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Long noncoding RNA TUSC7 inhibits cell proliferation, migration and invasion by regulating SOCS4 (SOCS5) expression
Xiaoling Wu1, Dongge Cai1, Fan Zhang1
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Background:
Long non-coding RNA (lncRNA) is emerging as an important regulator in various physiological and pathological processes. Recently, it was found that lncRNA long non-coding RNA tumor suppressor candidate 7 (TUSC7) could play tumor suppressive roles in several cancers. However, the function and underlying regulatory mechanism of lncRNA TUSC7 in endometrial carcinoma (EC) remains largely unclear.
Methods:
The expression levels of TUSC7 and microRNAs-616 (miR-616) were analyzed by real-time PCR and in situ hybridization. Cell cycle and cell metastasis associated protein expressions were determined by western blotting. Cell proliferation, cycle and metastasis were determined by CCK-8 cell viability, colony formation, flow cytometer, wound scratch and transwell assays respectively in vitro. RNA pull-down, luciferase and western blotting assays were used to examine the target relationship between TUSC7 and miR-616 or that between miR-616 and suppressors of cytokine signaling 4 (5) (SOCS4 (SOCS5)). The functional effects of TUSC7 through sponging miR-616 were further examined using a xenograft tumor mouse model in vivo.
Results:
TUSC7 was downexpressed in EC tissues and cell lines, and TUSC7 upregulation could remarkably inhibit cell proliferation, cycle progression and metastasis in EC cells. Mechanistic investigations demonstrated that TUSC7 can interact with miR-616 and decrease its expression, thereby upregulating the expression of miR-616's targets SOCS4 (SOCS5). Additionally, in vivo experiments using a xenograft tumor mouse model revealed that TUSC7 can serve as a tumor suppressor through sponging miR-616, and upregulating SOCS4 (SOCS5) in EC.
Conclusions:
In this study, a newly identified regulatory mechanism of lncRNA TUSC7/miR-616/ SOCS4 (SOCS5) axis was systematically studied, which may hold promise as a promising target for EC treatment.
Insights
Long non-coding RNA tumor suppressor candidate 7 (TUSC7) acts as a tumor suppressor in endometrial carcinoma by inhibiting proliferation and metastasis. TUSC7 targets miR-616, upregulating SOCS4/5, offering a potential therapeutic target for EC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are key regulators in biological processes.
- The lncRNA tumor suppressor candidate 7 (TUSC7) exhibits tumor-suppressive roles in various cancers.
- The specific function of TUSC7 in endometrial carcinoma (EC) and its regulatory mechanisms remain largely unknown.
Purpose of the Study:
- To investigate the role and mechanism of lncRNA TUSC7 in endometrial carcinoma.
- To elucidate the regulatory axis involving TUSC7, miR-616, and SOCS4/5 in EC.
- To assess the therapeutic potential of TUSC7 in EC treatment.
Main Methods:
- Quantitative real-time PCR and in situ hybridization for TUSC7 and miR-616 expression analysis.
- Western blotting to assess cell cycle and metastasis-associated protein expression.
- In vitro assays (CCK-8, colony formation, flow cytometry, wound scratch, Transwell) and in vivo xenograft mouse models to evaluate TUSC7 function.
- RNA pull-down, luciferase, and western blotting assays to confirm molecular interactions.
Main Results:
- TUSC7 was significantly downregulated in EC tissues and cell lines.
- TUSC7 upregulation suppressed EC cell proliferation, cell cycle progression, and metastasis.
- TUSC7 functions as a tumor suppressor by sponging miR-616, leading to the upregulation of its targets, SOCS4 and SOCS5.
- In vivo studies confirmed TUSC7's tumor-suppressive role via the miR-616/SOCS4/5 pathway.
Conclusions:
- A novel regulatory mechanism involving the lncRNA TUSC7/miR-616/SOCS4 (SOCS5) axis in endometrial carcinoma was identified.
- This regulatory axis represents a promising therapeutic target for endometrial carcinoma treatment.
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