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Long Noncoding RNA ADAMTS9-AS2 Inhibits the Proliferation, Migration, and Invasion in Bladder Tumor Cells
Zhan Zhang1, Jin-Peng Jia2, Yin-Jiang Zhang3
1Department of Rehabilitation Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Background:
Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA ADAMTS9-AS2 have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of ADAMTS9-AS2 in bladder tumor cells were explored in our study.
Materials And Methods:
Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the ADAMTS9-AS2 and ADAMTS9 expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of ADAMTS9-AS2 on proliferation, migration, and invasion in bladder tumor cells.
Results:
First, ADAMTS9-AS2 downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that ADAMTS9-AS2 expression was positively related to ADAMTS9, which is in accordance with the results from GEO database. Second, ADAMTS9-AS2 contributed to the inhibition of proliferation, migration, and invasion in bladder tumor cells. Third, ADAMTS9-AS2 was linked with PI3K/AKT/mTOR pathway related-molecules, several key autophagy, and apoptotic proteins.
Conclusion:
Conjointly, our findings suggested that ADAMTS9-AS2 might function as a tumor suppressor to restrain the proliferation, migration, and invasion in bladder tumor cells. The potential mechanism of ADAMTS9-AS2 related to PI3K/AKT/mTOR signal pathway was further identified. Of note, we found that ADAMTS9-AS2 has a significant effect on several key autophagy and apoptotic proteins. Therefore, these observations will provide supportive evidence to ADAMTS9-AS2 as a potential biomarker in patients with bladder tumor.
Insights
The long noncoding RNA ADAMTS9-AS2 acts as a tumor suppressor in bladder cancer. It inhibits cell proliferation, migration, and invasion, potentially via the PI3K/AKT/mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer is a prevalent malignancy with incompletely understood pathogenesis.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer, but many remain uncharacterized.
- The lncRNA ADAMTS9-AS2 has been implicated in various cancers, but its function in bladder cancer was unexplored.
Purpose of the Study:
- To investigate the role and potential mechanism of lncRNA ADAMTS9-AS2 in bladder tumor cells.
- To determine if ADAMTS9-AS2 expression correlates with bladder tumor progression.
- To explore ADAMTS9-AS2's impact on cell proliferation, migration, and invasion.
Main Methods:
- Quantitative real-time PCR and bioinformatic analyses to assess ADAMTS9-AS2 and ADAMTS9 expression.
- Western blot assays to evaluate protein levels of key molecules.
- Cell proliferation (CCK8, clonogenic assays), migration (scratch wound healing), and invasion (Transwell assays) were performed.
Main Results:
- ADAMTS9-AS2 was found to be downregulated in bladder tumor cells.
- Overexpression of ADAMTS9-AS2 suppressed proliferation, migration, and invasion.
- ADAMTS9-AS2 expression positively correlated with ADAMTS9 and was linked to the PI3K/AKT/mTOR pathway, autophagy, and apoptosis-related proteins.
Conclusions:
- ADAMTS9-AS2 functions as a tumor suppressor in bladder cancer, inhibiting cell proliferation, migration, and invasion.
- The mechanism involves regulation of the PI3K/AKT/mTOR pathway and key autophagy/apoptotic proteins.
- ADAMTS9-AS2 shows potential as a diagnostic biomarker for bladder cancer patients.
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