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Long noncoding RNA LINC00982 upregulates CTSF expression to inhibit gastric cancer progression via the transcription
Lei Zheng1, Junlin Cao1, Lijie Liu1
1Department of Oncology, the First Hospital of Qinhuangdao, Qinhuangdao, China.
Abstract:
Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer.NEW & NOTEWORTHY We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.
Insights
Long noncoding RNA LINC00982 acts as a tumor suppressor in gastric cancer by inhibiting proliferation and metastasis. It targets HEY1, promoting cathepsin F (CTSF) expression, offering a potential therapeutic target for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer malignancy is influenced by long noncoding RNAs (lncRNAs).
- The specific role and regulatory mechanisms of LINC00982 in gastric cancer remain unclear.
- Understanding lncRNA functions is crucial for developing novel cancer therapies.
Purpose of the Study:
- To elucidate the molecular mechanisms by which LINC00982 regulates gastric cancer cell malignancy.
- To investigate the interaction between LINC00982, HEY1, and CTSF in gastric cancer.
- To evaluate LINC00982 as a potential therapeutic target for gastric cancer.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blotting to assess LINC00982 and CTSF expression.
- Cellular assays including CCK-8, colony formation, Transwell migration, and invasion assays to evaluate LINC00982's functional effects.
- RNA-binding protein immunoprecipitation, luciferase assays, and chromatin immunoprecipitation to determine molecular interactions.
- In vivo tumor formation assays in a nude mouse model.
Main Results:
- LINC00982 expression was downregulated in gastric cancer tissues and cells.
- Overexpression of LINC00982 suppressed gastric cancer cell proliferation, migration, and invasion.
- LINC00982 directly bound to transcription factor HEY1, inhibiting its expression.
- LINC00982 promoted CTSF expression by disrupting HEY1 binding to the CTSF promoter.
- In vivo studies confirmed the tumor-suppressive role of LINC00982.
Conclusions:
- LINC00982 functions as a tumor suppressor in gastric cancer.
- The regulatory network involving LINC00982, HEY1, and CTSF provides insights into gastric tumorigenesis.
- LINC00982 represents a promising novel antitumor target for gastric cancer treatment.
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