MiR-125b-5p suppresses the bladder cancer progression via targeting HK2 and suppressing PI3K/AKT pathway
Shuo Liu1, Qin Chen2, Yue Wang2
1Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Number 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, People's Republic of China. lixiaonan827@163.com.
Abstract:
Bladder cancer (BCa) is identified as the most common malignant solid cancer in the urogenital tract. Recently, dysregulation of miRNAs has received more attention because of its extensive role in the carcinogenesis of BCa. This research was designed to verify how miR-125b-5p be involved in BCa development. The expression of miR-125b-5p was detected in 52 pairs of BCa specimens and adjacent normal bladder specimens. The effects of miR-125b-5p on BCa viability, migration, and apoptosis in vitro were examined. We then examined directly target gene(s) of miR-125b-5p in BCa cells. Our data demonstrated that miR-125b-5p was decreased in BCa tissues and cell lines. Patients with low miR-125b-5p expression had obviously shorter 5-year survival time. Lower miR-125b-5p expression was significant correlated with distant metastasis, tumor size and lymph node metastasis. Ectopic expression of miR-125b-5p inhibited the BCa cell viability and migration and induced cell apoptosis. Furthermore, HK2 was confirmed regulated by miR-125b-5p. HK2 recovered miR-125b-5p-mediated suppression of BCa cell viability and migration. In addition, miR-125b-5p also exhibited suppressive effect on PI3K/AKT pathway. Overall, these data indicate that miR-125b-5p played a role in the suppressive effect on BCa by targeting HK2 through suppressing PI3K/AKT pathway and offer a potential therapeutic target for BCa.
Insights
MicroRNA-125b-5p (miR-125b-5p) is downregulated in bladder cancer (BCa), inhibiting tumor growth and metastasis. Restoring miR-125b-5p shows therapeutic potential against BCa by targeting HK2 and the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer (BCa) is a prevalent malignancy in the urogenital tract.
- MicroRNAs (miRNAs) are increasingly recognized for their role in BCa development and progression.
- Dysregulation of specific miRNAs, like miR-125b-5p, is implicated in cancer carcinogenesis.
Purpose of the Study:
- To investigate the role of miR-125b-5p in bladder cancer (BCa) development.
- To determine the impact of miR-125b-5p expression on BCa cell behavior and patient survival.
- To identify direct target genes of miR-125b-5p in BCa cells.
Main Methods:
- Quantitative analysis of miR-125b-5p expression in 52 BCa tissue specimens and adjacent normal tissues.
- In vitro assays to assess the effects of miR-125b-5p on BCa cell viability, migration, and apoptosis.
- Identification and validation of direct target genes of miR-125b-5p, including HK2.
- Investigation of miR-125b-5p's influence on the PI3K/AKT signaling pathway.
Main Results:
- miR-125b-5p expression was significantly decreased in BCa tissues and cell lines compared to normal controls.
- Low miR-125b-5p expression correlated with shorter 5-year survival, distant metastasis, larger tumor size, and lymph node metastasis.
- Overexpression of miR-125b-5p inhibited BCa cell viability and migration while promoting apoptosis.
- HK2 was identified as a direct target of miR-125b-5p, and its restoration counteracted the suppressive effects of miR-125b-5p.
- miR-125b-5p demonstrated a suppressive effect on the PI3K/AKT pathway.
Conclusions:
- miR-125b-5p acts as a tumor suppressor in bladder cancer (BCa).
- The tumor-suppressive function of miR-125b-5p is mediated by targeting HK2 and inhibiting the PI3K/AKT pathway.
- miR-125b-5p represents a potential therapeutic target for bladder cancer treatment.
