Long non-coding RNA HOTAIR is targeted and regulated by miR-141 in human cancer cells

Area of Science:

• Molecular Biology
• Genetics
• Oncology

Background:

• Long non-coding RNA HOTAIR interacts with the polycomb repressive complex, suppressing target genes and promoting cancer malignancy.
• MicroRNA-141 (miR-141) is implicated in epithelial-mesenchymal transition and its expression inversely correlates with cancer invasiveness.
• A negative correlation between HOTAIR and miR-141 expression was observed in renal carcinoma cells.

Purpose of the Study:

• To investigate the regulatory relationship between HOTAIR and miR-141 in human cancer cells.
• To elucidate the mechanism by which miR-141 affects HOTAIR expression and function.
• To determine the role of the Ago2 complex in this interaction.

Main Methods:

• Analysis of HOTAIR and miR-141 expression correlation in renal carcinoma cells.
• Assessment of HOTAIR's effects on cancer cell proliferation and invasion.
• Investigation of miR-141 binding to HOTAIR and its impact on HOTAIR expression and function.
• Co-immunoprecipitation assays to detect HOTAIR and miR-141 association with the Ago2 complex.
• In vitro cleavage assays to confirm Ago2-dependent degradation of HOTAIR.

Main Results:

• HOTAIR expression was inversely correlated with miR-141 expression in renal carcinoma.
• HOTAIR was found to promote cancer cell proliferation and invasion.
• miR-141 directly binds to HOTAIR, suppressing its expression and inhibitory functions on proliferation and invasion.
• Both HOTAIR and miR-141 were found in the Ago2 complex, and Ago2 mediated HOTAIR cleavage in the presence of miR-141.

Conclusions:

• miR-141 suppresses HOTAIR-driven malignancy in human cancer cells.
• The suppression of HOTAIR by miR-141 is dependent on the Ago2 complex, involving sequence-specific binding and subsequent cleavage.
• This study reveals a novel Ago2-dependent regulatory pathway where miR-141 acts as a tumor suppressor by targeting HOTAIR.