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Long Noncoding RNA MNX1 antisense RNA 1 Exerts Oncogenic Functions in Bladder Cancer by Regulating miR-218-5p/RAB1A
Jun Wang1, Huiwu Xing1, Abdul Aziz Nikzad1
1Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Abstract:
LncRNA MNX1 antisense RNA 1 (MNX1-AS1) is significantly overexpressed in patients with bladder cancer, suggesting that it might be associated with bladder cancer. However, the molecular mechanism of MNX1-AS1 in bladder cancer remained indistinct. To illustrate the role of MNX1-AS1 in bladder cancer, the gain- and loss-of-function experiments were conducted in bladder cancer cells. Reduced expression of MNX1-AS1 could suppress cell proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer cells, whereas overexpression of MNX1-AS1 resulted in the opposite effects. Mechanistic analysis demonstrated that miR-218-5p was a direct target of RAB1A. MNX1-AS1 could competitively bind to miR-218-5p to regulate RAB1A expression in bladder cancer cells. Furthermore, in vivo experiments revealed that reduced expression of MNX1-AS1 inhibited tumor growth and metastasis. Taken together, MNX1-AS1 functions as a sponge to miR-218-5p to modulate RAB1A expression in bladder cancer, which suggests that MNX1-AS1 might serve as a novel therapeutic target and a novel biomarker for metastasis and prognosis in bladder cancer. SIGNIFICANCE STATEMENT: Our study demonstrates that long noncoding RNA MNX1-AS1 promotes the initiation and progression of bladder cancer. MNX1-AS1 regulates RAB1A expression to promote proliferation, migration, invasion, and epithelial-mesenchymal transitions of bladder cancer cells via miR-218-5p, which contributes to the tumor growth and metastasis of bladder cancer. Collectively, these results suggest that MNX1-AS1 might serve as a potential biomarker for bladder cancer.
Insights
Long noncoding RNA MNX1-AS1 promotes bladder cancer progression by regulating RAB1A expression via sponging miR-218-5p. Reduced MNX1-AS1 inhibits proliferation, migration, invasion, and metastasis, suggesting it as a therapeutic target and biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNA MNX1 antisense RNA 1 (MNX1-AS1) is overexpressed in bladder cancer.
- The precise molecular mechanisms of MNX1-AS1 in bladder cancer remain unclear.
Purpose of the Study:
- To elucidate the role and molecular mechanism of MNX1-AS1 in bladder cancer progression.
- To investigate MNX1-AS1 as a potential therapeutic target and biomarker for bladder cancer.
Main Methods:
- Gain- and loss-of-function experiments were performed in bladder cancer cell lines.
- Mechanistic studies involved assessing the interaction between MNX1-AS1, miR-218-5p, and RAB1A.
- In vivo experiments using mouse models were conducted to evaluate tumor growth and metastasis.
Main Results:
- Reduced MNX1-AS1 expression suppressed bladder cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- Overexpression of MNX1-AS1 exhibited opposite effects, promoting these malignant phenotypes.
- MNX1-AS1 acts as a molecular sponge for miR-218-5p, thereby regulating RAB1A expression.
- In vivo, decreased MNX1-AS1 expression inhibited tumor growth and metastasis.
Conclusions:
- MNX1-AS1 promotes bladder cancer initiation and progression by modulating the miR-218-5p/RAB1A axis.
- MNX1-AS1 may serve as a novel therapeutic target and a potential biomarker for bladder cancer metastasis and prognosis.
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