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Published on: January 22, 2021
Ultrasound microbubble-mediated miR-503-5p downregulation suppressed in vitro CRC progression via promoting SALL1
Yaru Wang1, Yanting Li2, Xin Li2
1Department of Colorectal Surgery, Baoji Central Hospital, China.
Background:
This study compared the effect of ultrasound microbubble-mediated miR-503-5p downregulation with that of pure liposome-mediated miR-503-5p downregulation on colorectal cancer (CRC) progression and explored the downstream mechanism.
Methods:
Bioinformatics tools were utilized to predict miR-503-5p-targeted genes and CRC progression-associated genes. MiR-503-5p and sal-like 1 (SALL1) expressions in CRC cells and tissues were analyzed by qRT-PCR and/or bioinformatics tools; their correlations with overall survival and clinicopathological features of CRC patients were presented, and their interaction was validated by dual-luciferase reporter assay. CRC cells received ultrasound microbubble-mediated miR-503-5p downregulation and/or liposome-mediated miR-503-5p downregulation or SALL1 silencing. Cell phenotype changes were evaluated by flow cytometry, as well as MTT, Wound healing, Transwell and tube formation assays. E-cadherin, N-cadherin, Vimentin, B-cell lymphoma (Bcl)- 2, Cleaved caspase-3, and SALL1 expressions in cells were analyzed by Western blot.
Results:
Upregulated miR-503-5p in CRC tissues and cells was detected, associated with poorer cell differentiation, easier lymph node metastasis and higher TNM stages, and related to poorer prognoses of CRC patients. Ultrasound microbubble-mediated miR-503-5p downregulation relative to pure liposome-mediated miR-503-5p downregulation better decreased viability, inhibited migration, invasion and tube formation, enhanced apoptosis, upregulated SALL1, E-cadherin and Cleaved caspase-3, and downregulated miR-503-5p, N-cadherin, Vimentin and Bcl-2 in CRC cells. SALL1 was targeted by miR-503-5p, low-expressed in CRC tissues and cells and positively related to CRC patients' survival. Silencing SALL1 exerted the opposite effects, which reversed the effects of ultrasound microbubble-mediated miR-503-5p downregulation and vice versa.
Conclusion:
Ultrasound microbubble-mediated miR-503-5p downregulation suppressed in vitro CRC progression via promoting SALL1 expression.
