Hsa-miR-30a-3p overcomes the acquired protective autophagy of bladder cancer in chemotherapy and suppresses tumor growth and muscle invasion.
Thomas I-Sheng HwangPo-Chun ChenTe-Fu TsaiJi-Fan LinKuang-Yu ChouChao-Yen HoHung-En ChenAn-Chen ChangPublished in: Cell death & disease (2022)
Bladder cancer (BC) is the second most common urologic cancer in western countries. New strategies for managing high-grade muscle-invasive bladder cancer (MIBC) are urgently required because MIBC has a high risk of recurrence and poor survival. A growing body of evidence indicates that microRNA has potent antitumorigenic properties in various cancers, and thus, therapeutic strategies based on microRNA may show promising results in cancer therapy. Analysis of The Cancer Genome Atlas (TCGA) database indicated that hsa-miR-30a-3p is downregulated in human BC. Our in vitro investigation demonstrated that hsa-miR-30a-3p suppresses the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 and reduces the cell invasive potential of BC cells. Furthermore, hsa-miR-30a-3p directly targets ATG5, ATG12, and Beclin 1; this in turn improves the chemosensitivity of BC cells to cisplatin through the repression of protective autophagy. In a tumor-xenograft mice model, hsa-miR-30a-3p suppressed muscle invasion. Cotreatment with hsa-miR-30a-3p enhanced the antitumor effect of cisplatin in reducing tumor growth in BC. The current study provides a novel strategy of using hsa-miR-30a-3p as an adjuvant or replacement therapy in future BC treatment.
Keyphrases
- induced apoptosis
- signaling pathway
- replacement therapy
- high grade
- cell death
- muscle invasive bladder cancer
- endoplasmic reticulum stress
- cell migration
- papillary thyroid
- cell cycle arrest
- cancer therapy
- oxidative stress
- skeletal muscle
- single cell
- south africa
- early stage
- squamous cell
- low grade
- gene expression
- long non coding rna
- cell therapy
- radiation therapy
- pi k akt
- sensitive detection
- lymph node metastasis
- living cells