circRNA mannosidase alpha class 1A member 2 contributes to the proliferation and motility of papillary thyroid cancer cells through upregulating metadherin via absorbing microRNA-449a

Abstract

Papillary thyroid carcinoma (PTC) is a common malignancy in endocrine system globally. Accumulating articles have found that circular RNAs (circRNAs) were dysregulated, and they were involved in PTC development. The aim of this project was to explore the function and associated mechanism of circRNA mannosidase alpha class 1A member 2 (circMAN1A2) in PTC progression. The expression of RNA was determined by real-time quantitative PCR. Cell proliferation ability was analyzed by colony formation assay and 5-ethynyl-2′-deoxyuridine assay. Cell migration and invasion were assessed by wound healing assay and transwell invasion assay, respectively. Protein levels were determined by Western blot assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were applied to confirm the interaction between microRNA-449a (miR-449a) and circMAN1A2 or metadherin (MTDH). Xenograft tumor model was utilized to explore the effect of circMAN1A2 silencing on tumor growth in vivo. CircMAN1A2 expression was elevated in PTC specimens and three PTC cell lines relative to adjacent normal specimens and Nthy-ori 3-1 cell line. CircMAN1A2 silencing inhibited the proliferation and motility of PTC cells. CircMAN1A2 acted as a molecular sponge of miR-449a, and circMAN1A2 knockdown suppressed PTC development partly through upregulating miR-449a. MiR-449a bound to the 3′ untranslated region of MTDH, and miR-449a restrained PTC progression partly through down-regulating MTDH. CircMAN1A2 interference suppressed PTC progression in vivo. CircMAN1A2 contributed to the proliferation ability and motility of PTC cells through enhancing MTDH expression via sponging miR-449a.

The potential of cricMAN1A2 as a novel biomarker for gout diagnosis

“…We predicted has-miR-1297, has-miR-4465 and has-miR-26b-5p were related to has_circMAN1A2_011 and MAN1A2 is the target genes. Studies states that circMAN1A2 contributes to the proliferation and motility of papillary thyroid cancer cells through upregulating metadherin via absorbing microRNA-449a [33]. Based on those evidence, we speculate that has_circMAN1A2_011 may affect modulate MAN1A2 assembly through acting as those three miRNA sponges, but there have not any reports regarding relationship between circRNAs and gout, in addition, the role of circRNAs involving in the pathogenesis of gout is not well understood, so our speculate for the mechanism of action needs further study.…”

Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto’s thyroiditis using bioinformatics methods

“…MiR-506-3p may inhibit PTC proliferation by suppressing YAP1 expression and regulating the YAP1-CDK2/Cy clinical E1 cell cycle pathway ( 77 ). MiR-449a may partially inhibit PTC progression by downregulating metamucin (MTDH) ( 78 ). Numerous miRNAs targeting ABR hold diagnostic and therapeutic significance for PTC, and the ABR gene, as one of the prognostic genes of PTC, has not been targeted in relevant studies and deserves further exploration.…”

Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

“…MAN1A2 and VRK1 genes were dysregulated in both cell lines by different drugs. CircMAN1A1 is a marker of active cell proliferation in several types of tumors [ 29 , 30 ], and it is associated with cell motility, which is inhibited by its silencing [ 30 ]. In contrast, VRK1 is a kinase that phosphorylates several targets in the nucleus, and its expression is upregulated in BC and seems to promote epithelial-mesenchymal transition [ 31 ].…”

“…We underline that the deregulation of this specific pathway might depend on mutated-TP53, to which it seems attributed new unknown functions. In this case, the effects of AZD7762 could sustain the aggressiveness, occurring together with an increase also of circ/linHIPK3 ratio, correlating with poor survival in other types of tumors [ 39 ], as well as an increase of circ/linMAN1A2 associated with cell migration [ 30 ]. In MDA-MB-231 cells AURKA/B inhibitor GSK1070916 affected some RNAs in common with AZD7762.…”