Abstract
Background Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.
Highlights
Thyroid cancer is the most common type of human malignancies in endocrine system and is histologically categorized into papillary, follicular, medullary, anaplastic, and poorly differentiated thyroid cancer [1, 2], among which, papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinomas with a rising prevalence at an average annual rate of nearly 4% in recent years [1, 2]
We investigated the function of circLDLR in PTC carcinogenesis in vitro and in vivo and evaluated whether circLDLR exerted it biological functions via circLDLR/miR-637/LIM-only protein 4 (LMO4) in regulating cell biological behaviors of PTC
Patients with PTC were divided into two groups depending on the median level of circLDLR expression, and we found that patients in the high circLDLR group had a significantly shorter overall survival than those in the low circLDLR group (Figure 1(b))
Summary
Thyroid cancer is the most common type of human malignancies in endocrine system and is histologically categorized into papillary, follicular, medullary, anaplastic, and poorly differentiated thyroid cancer [1, 2], among which, papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinomas with a rising prevalence at an average annual rate of nearly 4% in recent years [1, 2]. Previous studies revealed that abnormal expression of circRNAs is drawn into the initiation and progression of PTC through by affecting the malignant behaviors of cancer cells [10, 11]. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). The function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. CircLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment
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