Title:LncRNA LINC00847 Accelerates Melanoma Progression by Regulating
MiR-133a-3p/TGFBR1 Axis
Volume: 27
Issue: 8
Author(s): Lei Jiang, Xiufang Shi, Yanxin Liu and Huaxia Chen*
Affiliation:
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong
First Medical University, Jinan, 250021, China
Keywords:
Skin melanoma, LINC00847 knockdown, dual-luciferase reporter assay, miR-133a-3p, TGFBR1, malignant tumor behavior, transfection.
Abstract:
Aims: Growing evidence has suggested that lncRNAs play a regulatory role in tumorigenesis.
Dysregulation of a newly identified lncRNA (LINC00847) has been involved in several
tumors. Nevertheless, the expression and roles of lncRNAs in skin melanoma remain unclear.
Therefore, we attempted to investigate the expressions and roles of lncRNAs in this study.
Materials and Methods: Expression levels of LINC00847 were quantified in tissue samples from
the TCGA database and clinically recruited participants. LINC00847 was inhibited in cells by
transfecting with si-LINC00847 or si-NC. Expressions of LINC00847 and miR-133a-3p were determined
using RT-qPCR, and the TGFBR1 level was determined using Western blotting. Targeting
sites of LINC00847 with miR-133a-3p and miR-133a-3p with TGFBR1 were predicted by bioinformatic
tools and proved by dual-luciferase reporter system and RNA immunoprecipitation. Cell
proliferation, invasion, and migration abilities were assessed using CCK8, cell colony formation,
cell wound scratch, and transwell assay, respectively.
Results: In both TCGA and clinical cohorts, the expression of LINC00847 was abnormally upregulated
in skin melanoma tissues than that of benign nevus. Besides, LINC00847 expression increased
more markedly in A375 and SK-MEL-28 cells than in normal epidermal melanocytes
(HEMa-LP cells). LINC00847 knockdown remarkably restrained skin melanoma cell proliferation,
metastasis, and wound healing rate. Furthermore, miR-133a-3p/TGFBR1 was the downstream target
for LINC00847. LINC00847 negatively regulated miR-133a-3p expression in skin melanoma
cells. Both miR-133a-3p inhibitors and TGFBR1 vector transfection reversed the effect of
LINC00847 silence in skin melanoma cells.
Conclusion: LINC00847 was highly expressed in skin melanoma, and its overexpression accelerated
the malignant tumor behavior of skin melanoma cells. The miR-133a-3p /TGFBR1 axis was
involved in the roles of LINC00847 in skin melanoma.