Abstract
Growing evidence has suggested that long noncoding RNAs (lncRNAs) play an essential role in the progression of papillary thyroid cancer (PTC). LncRNA LINC00311 was found to be able to regulate many cellular process in several diseases. However, the function and regulatory mechanism of LINC00311 remains unclear in PTC. In the present study, the results showed that the expression of LINC00311 was upregulated in PTC tissues and cells. Furthermore, knockdown of LINC00311 dramatically suppressed spheroid formation, proliferation, migration, and invasion in PTC cells in vitro. Mechanistic investigations revealed that LINC00311 was negatively correlated with the expression of miR‐330‐5p, meanwhile, TLR4 was a direct target of miR‐330‐5p. In addition, rescue assays further determined that LINC00311 contributed to the progression of PTC through regulating TLR4 expression. Taken together, these findings indicated that LINC00311 could promote cancer stem‐like properties by targeting miR‐330‐5p/TLR4 pathway in PTC.
Highlights
Thyroid cancer has gradually become one of the most malignant cancers over the past decades in the world.[1]
Our results demonstrated that cells transfected with sh-LINC00311 showed a slower closing of scratch wound and less invasion cell numbers compared with control vector in ALDH+ SNU-790 and TPC-1 cell lines, suggesting that knockdown of LINC00311 inhibited cell migration and invasion in papillary thyroid cancer (PTC) cells (P < .05, P < .01, Figure 3C,D)
The results showed that the expression of LINC00311 and mRNA toll-like receptors 4 (TLR4) was markedly downregulated, while the expression of miR330-5p was significantly increased when transfected with short hairpin RNA (shRNA) LINC00311 compared with shRNA LINC00311 or control plasmid (shNC) (P < .01, Figure 7A)
Summary
Thyroid cancer has gradually become one of the most malignant cancers over the past decades in the world.[1]. More and more evidence suggested that lncRNAs were involved in the regulation a wide range of cellular processes, and more importantly, play different roles in cancer stem-like properties.[18,19,20] For instance, lncRNA LUCAT1 plays an essential role in regulating breast cancer stemness.[21] Another lncRNA NEAT1 has been shown to promote stem-like properties in glioma cells.[22] In addition, microRNAs (miRNAs) are defined as small, noncoding RNAs, which are approximately 21 nucleotides long and are able to repress translation or degradation of mRNA.[23,24] Accumulating evidences have proved that lncRNAs and miRNAs were abnormally expressed in PTC and can be used to determine the outcomes of PTC patients.[25,26,27,28] Recent studies reported that lncRNA LINC00311 participates in the process of cell proliferation and differentiation.[29,30] it is still unclear whether certain lncRNAs contribute to stem-like properties in PTC cells. We want to clarify the related miRNA and the related pathways involved in stem-like properties in PTC cells These findings may provide a novel sight into the pathologic mechanism of PTC and might provide new therapeutic strategies
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