Broad-spectrum metastasis suppressing compounds and therapeutic uses thereof in human tumors

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• A novel human metastasis-inducing long non-coding RNA (lncRNA), SKAI1BC, was identified.
• SKAI1BC suppresses the KAI1/CD82 metastasis-suppressing gene and is upregulated in triple-negative breast cancer and melanoma cell lines.

Purpose of the Study:

• To identify small molecule compounds that bind and inhibit the SKAI1BC lncRNA.
• To evaluate the efficacy of these compounds in inhibiting metastasis and cell migration across various human cancers.
• To elucidate the mechanism of action, including the potential restoration of KAI1/CD82 expression.

Main Methods:

• Computational modeling of SKAI1BC lncRNA secondary structure.
• Screening of potential interacting compounds using the Inforna database.
• In vitro testing of identified compounds for inhibition of metastasis and cell migration in eight human cancer cell lines.
• Analysis of compound-induced changes in KAI1/CD82 RNA levels.

Main Results:

• Several compounds were identified that bind the SKAI1BC lncRNA.
• These compounds demonstrated inhibition of metastasis and cell migration in all eight tested solid human cancer types.
• The mechanism of action for several compounds involved enhancing KAI1/CD82 RNA levels, depending on the cancer type.
• This represents the first instance of using lncRNA structure modeling and compound interaction databases to discover potential small molecule drugs.

Conclusions:

• Novel small molecule compounds targeting SKAI1BC lncRNA can inhibit metastasis and cell migration in multiple human cancers.
• The compounds' mechanism involves restoring KAI1/CD82 expression, suggesting broad therapeutic potential.
• This study establishes a new paradigm for drug discovery by integrating lncRNA structural modeling with compound screening.