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Published on: September 3, 2021
lncSLERT Promotes Liver Metastasis in Colorectal Cancer by Down-Regulating HUNK Expression via RBM15-Mediated m6A
Lin Wang1, Liming Zhao2, Jialiang Liu2
1The State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Background:
Metastasis is a hallmark of cancer and the leading cause of cancer-related mortality. However, the mechanism underlying liver metastasis in colorectal cancer (CRC) remains incompletely understood. This study explores the role of long non-coding RNA (lncRNA) SLERT in promoting CRC liver metastasis by downregulating HUNK expression.
Methods:
SLERT expression levels in CRC tissues were analyzed and correlated with patient survival outcomes. Functional assays, including migration and invasion assays, were performed to assess the impact of SLERT knockdown and overexpression on metastatic behavior. Mechanistic studies examined SLERT's interaction with the RNA-binding protein RBM15 and its effect on HUNK mRNA stability. The subcellular localization of SLERT was also determined.
Results:
SLERT was significantly upregulated in CRC tissues and associated with poor survival outcomes. Silencing SLERT inhibited CRC cell migration and invasion, whereas its overexpression enhanced these metastatic properties. Mechanistically, SLERT interacted with RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK expression and increased metastatic potential. SLERT was primarily localized in the cytoplasm, indicating its active role in gene regulation within the tumor microenvironment.
Conclusion:
LERT promotes liver metastasis in CRC by downregulating HUNK expression through RBM15-mediated mRNA destabilization. These findings suggest that SLERT could serve as a diagnostic biomarker and therapeutic target. Targeting SLERT or restoring HUNK expression may provide novel strategies to combat CRC liver metastasis and improve patient prognosis.
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