MiR-29b-3p Inhibits Migration and Invasion of Papillary Thyroid Carcinoma by Downregulating COL1A1 and COL5A1

Abstract

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that regulate genetic expression and are also vital for tumor initiation and development. MiR-29b-3p was found to be involved in regulating various biological processes of tumors, including tumor cell proliferation, metastasis, and apoptosis inhibition; however, the biofunction and molecule-level mechanisms of miR-29b-3p inpapillary thyroid carcinoma (PTC) remain unclear.MethodsThe expression of miR-29b-3p in PTC samples was tested via qRT-PCR. Cellular proliferation was analyzed by CCK-8 and EdU assays, and cellular migratory and invasive abilities were assessed utilizing wound-healing and Transwell assays. In addition, protein expressions of COL1A1, COL5A1, E-cadherin, N-cadherin, Snail, and Vimentin were identified via Western blot (WB) assay. Bioinformatics, qRT-PCR, WB, and dual luciferase reporter assays were completed to identify whether miR-29b-3p targeted COL1A1 and COL5A1. In addition, our team explored the treatment effects of miR-29b-3p on a murine heterograft model.ResultsOur findings revealed that miR-29b-3p proved much more regulated downward in PTC tissue specimens than in adjacent non-cancerous tissues. Meanwhile, decreased expression of miR-29b-3p was strongly related to the TNM stage of PTC patients (p<0.001), while overexpression of miR-29b-3p in PTC cells suppressed cellular migration, invasion, proliferation, and EMT. Conversely, silencing miR-29b-3p yielded the opposite effect. COL1A1 and COL5A1 were affirmed as the target of miR-29b-3p. Additionally, the COL1A1 and COL5A1 were highly expressed in PTC tumor samples than in contrast to neighboring healthy samples. Functional assays revealed that overexpression of COL1A1 or COL5A1 reversed the suppressive role of miR-29b-3p in migration, invasion, and EMT of PTC cells. Finally, miR-29b-3p agomir treatment dramatically inhibited Xenograft tumor growth in the animal model.ConclusionsThese findings document that miR-29b-3p inhibited PTC cells invasion and metastasis by targeting COL1A1 and COL5A1; this study also sparks new ideas for risk assessment and miRNA replacement therapy in PTC.

Differential microRNA expression for diagnosis and prognosis of papillary thyroid cancer

“…miRNAs like miR-375, miR-203, miR-29b-3p, and miR-369-3p were downregulated, whereas their target genes ERBB2, AKT3, COL1A1, and TSPAN13 were overexpressed. Tumor development, metastasis, apoptosis, and cell invasion are some of the processes in which these genes are involved ( 13 , 17 , 20 , 21 ).…”

CMTM7 inhibits breast cancer progression by regulating Wnt/β-catenin signaling

“…The dysregulation of miRNAs on their target genes in cancer progression has become the research hotspot in recent years [ 36 ]. The miR-29b-3p inhibited thyroid cancer invasion and migration by regulating COL1A1 and COL5A1 [ 37 ]. The miR-520a-5p plays an essential role in regulating gemcitabine resistance by directly targeting PPP5C in pancreatic cancer [ 38 ].…”

The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway

“…The p53 protein family is unanimously associated with the metastatic dissemination in various cancers, but depending on the cells involved, on the isoforms and on the context, it can be associated with an inhibitory role or an inducing role [ 27 , 41 , 55 ]. MicroRNAs appear to be frequently involved at various levels in this regulatory process [ 32 , 45 ], sometimes upstream and sometimes downstream of the p63 and/or p73 proteins [ 27 , 55 ]. The numerous different isoforms for p63 and p73 that are associated with the TGFβ implication in this process adds even more complexity because of its well-known dual effect, and this is probably one of the reasons why we observe so many discrepancies in the literature regarding the pro- or anti-metastatic effect of p63 and p73.…”

“…An emerging consensus is that miRNAs are particularly prominent within regulatory circuits controlling transcription factor functions, as it happens in the p53 protein family. Although we are only beginning to uncover their complexity, such circuits may be particularly important within the regulation of metastasis [ 27 , 32 , 44 , 45 , 46 ].…”