Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma

Czajka, Agnieszka; Wójcicka, Anna; Klinke, Anna; Kotlarek, Marta; Bakuła-Zalewska, Elwira; Koperski, Łukasz; Wiechno, W; Jażdżewski, Krystian

doi:10.1371/journal.pone.0151968

Cited by 49 publications

(34 citation statements)

References 35 publications

(42 reference statements)

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“…Reduced RARβ and increased activity of ALDH enzyme have been previously associated with increased miR-146b-5p [30] that was also con rmed in the present study. Additionally, miR-378a-5p overexpression in a rat cardiomyocyte study was associated with ALDH2 downregulation therefore downregulation of miR-378a-5p (Figure 2A) in the present work supported upregulation of ALDH2 in our initial array ( Figure 1A) [31].…”

Section: Resultssupporting

confidence: 91%

Normalization of enzyme expression and activity regulating vitamin A metabolism increases RAR-beta expression and reduces cellular migration in diseases caused by tuberous sclerosis gene mutations

Abdelwahab

Bovari-Biri

Smuk

et al. 2020

Preprint

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Background Mutation in a tuberous sclerosis gene (TSC1 or 2) leads to continuous activation of the mammalian target of rapamycin (mTOR). mTOR activation alters various cellular functions including cellular metabolism. In association with altered metabolism, several studies have shown reduced retinoic acid receptor beta (RARβ) expression. Investigation of the altered metabolic process can offer the identification of novel therapeutic targets and therapeutic strategies in diseases caused by TSC mutation with limited treatment options. Methods RARβ expression, metabolic enzymes expression and activity were assessed in human kidney angiomyolipoma cell line, primary lymphangioleiomyomatosis (LAM) tissue derived LAM cell lines as well as primary LAM lung tissue sections. TaqMan arrays, enzyme activities, qRT-PCRs, immunohistochemistry, immunofluorescent staining, Western blotting and metabolic enzyme regulating miRNAs were analysed. The functional effects of retinoic acid (RA) and rapamycin were tested in a scratch assay and in a 3D aggregate tissue system to assess the ability of cell migration. Results Metabolic enzyme arrays revealed a general deregulation of many enzymes involved in vitamin A metabolism including aldehyde dehydrogenases (ALDHs), alcohol dehydrogenases (ADHs) and Cytochrome P450 2E1 (CYP2E1). Furthermore, RARβ downregulation was a characteristic feature of all TSC-deficient cells and tissues. Combination of the two FDA approved drugs -RA for acute myeloid leukaemia and rapamycin for TSC mutation- normalised metabolic enzyme activity, restored RARβ expression and reduced cellular migration. Conclusion Deregulation of vitamin A metabolizing enzymes is a feature of TSC mutation. RA can normalize RARβ levels and limit migration. Combination of RA with reduced dose of rapamycin might be able to decrease adverse effects of rapamycin offering an alternative treatment for patients with TSC mutation.

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Section: Resultssupporting

confidence: 91%

Normalization of enzyme expression and activity regulating vitamin A metabolism increases RAR-beta expression and reduces cellular migration in diseases caused by tuberous sclerosis gene mutations

Abdelwahab

Bovari-Biri

Smuk

et al. 2020

Preprint

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“…miRNAs are thought to activate the suppress function on the target gene by the complementary pairing between the sequence of target mRNA and the subsequences completely or in part [13]. There are many studies showing that miRNA is the important part of tumorigenesis; it has been demonstrated that many kinds of miRNAs have the function in cancer promotion or cancer suppression [14–16]. At present, the studies have proved that miR-940 was significantly downregulated in malignant tumors, such as gastric cancer and prostate cancer, through the regulation of malignant tumor apoptosis and the suppression of malignant tumor migration.…”

Section: Discussionmentioning

confidence: 99%

miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma

Ding

Zhang

Yang

et al. 2016

BioMed Research International

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Aim. To investigate the expression of miR-940 in the hepatocellular carcinoma (HCC) and its impact on function and biological mechanism in the HCC cells. Methods. Quantitative RT-PCR analysis was used to quantify miR-940 expression in 46 cases of tissues and cells. Transfection of HCC cell lines was performed by miR-940 mimics; the abilities of invasion and migration were assessed through Transwell array. Western blot represents the alteration in expression of CXCR2 by miR-940 mimics. Results. miR-940 expression was decreased significantly in the HCC tissues and the relevant cell lines. miR-940 upregulation suppressed the invasion and migration of HCC cells in vitro. Furthermore, the CXCR2 was downregulated to suppress invasion and migration after miR-940 mimics. Moreover, decreased miR-940 expression was negatively correlated with Edmondson grade (P = 0.008), tumor microsatellite or multiple tumors (P = 0.04), vascular invasion (P = 0.035), and recurrence and metastasis (P = 0.038). Kaplan-Meier analysis demonstrated that decreased miR-940 expression contributed to poor overall survival (P < 0.05). Conclusions. Our findings present that miR-940 acts as a pivotal adaptor of CXCR2 and its transcription downregulated CXCR2 expression to decrease HCC invasion and migration in vitro. Our study suggests that miR-940 may be a novel poor prognostic biomarker for HCC.

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“…Moreover, targeting miR-106a with antagomir increases the expression of NIS and TSHR while sensitizing ATC cells to radioiodine treatment (25). Interestingly, miR-146b regulates the expression of RARβ (26) and serum miR-146b levels are also associated with thyroid tumors poor prognosis (27).…”

Section: Microrna and Thyroid Follicular Cell Differentiationmentioning

confidence: 99%

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

Fuziwara

Saito

Kimura

2019

Archives of Endocrinology and Metabolism

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Thyroid cancer has been rapidly increasing in prevalence among humans in last 2 decades and is the most prevalent endocrine malignancy. Overall, thyroid-cancer patients have good rates of long-term survival, but a small percentage present poor outcome. Thyroid cancer aggressiveness is essentially related with thyroid follicular cell loss of differentiation and metastasis. The discovery of oncogenes that drive thyroid cancer (such as RET, RAS, and BRAF), and are aligned in the MAPK/ERK pathway has led to a new perspective of thyroid oncogenesis. The uncovering of additional oncogenemodulated signaling pathways revealed an intricate and active signaling cross-talk. Among these, microRNAs, which are a class of small, noncoding RNAs, expanded this cross-talk by modulating several components of the oncogenic network-thus establishing a new layer of regulation. In this context, TGFβ signaling plays an important role in cancer as a dual factor: it can exert an antimitogenic effect in normal thyroid follicular cells, and promote epithelial-to-mesenchymal transition (EMT), cell migration, and invasion in cancer cells. In this review, we explore how microRNAs influence the loss of thyroid differentiation and the increase in aggressiveness of thyroid cancers by regulating the dual function of TGFβ. This review provides directions for future research to encourage the development of new strategies and molecular approaches that can improve the treatment of aggressive thyroid cancer.

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Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma

Cited by 49 publications

References 35 publications

Normalization of enzyme expression and activity regulating vitamin A metabolism increases RAR-beta expression and reduces cellular migration in diseases caused by tuberous sclerosis gene mutations

Normalization of enzyme expression and activity regulating vitamin A metabolism increases RAR-beta expression and reduces cellular migration in diseases caused by tuberous sclerosis gene mutations

miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

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