miR‑122‑5p suppresses the oncogenesis of PTC by inhibiting DUSP4 expression

Abstract

MicroRNAs (miRNAs or miRs) play an important role in regulating the occurrence and development of papillary thyroid carcinoma (PTC). miR-122-5p is widely considered a tumour inhibitor, which has not been fully explored in PTC. Bioinformatics analysis identified dual specificity phosphatase 4 (DUSP4), a tumour promoter gene for PTC, as a downstream target of miR-122-5p. The aim of the present study was to investigate the role and molecular mechanism of miR-122-5p in PTC oncogenesis. In this study, the expression pattern of miR-122-5p in PTC cancer tissues and PTC cell lines was investigated via reverse transcription-quantitative PCR. Furthermore, the roles of miR-122-5p in PTC were explored using gain-of-function and loss-of-function assays. The results revealed that the expression of miR-122-5p was significantly lower in PTC cancer tissues, especially in cancer tissues with significant invasion or metastasis. Overexpression of miR-122-5p caused by miR-122-5p mimics inhibited the proliferation, invasion, and migration of the PTC cell line K1, while knockdown of miR-122-5p by miR-122-5p inhibitors exhibited the opposite effect. Furthermore, in vivo assays revealed that miR-122-5p overexpression inhibited tumour growth. In addition, miR-122-5p was negatively correlated with DUSP4 expression in PTC cancer tissues. miR-122-5p overexpression inhibited DUSP4 expression in K1 cells, while miR-122-5p downregulation produced the inverse effect. Specifically, a luciferase reporter assay confirmed the binding sites of miR-122-5p on the 3'-UTR of DUSP4, demonstrating the targeting effect of miR-122-5p on DUSP4. miR-122-5p inhibited the oncogenesis of PTC by targeting DUSP4, revealing the potential application value of miR-122-5p in the diagnosis and treatment of PTC.

Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

“…DUSP4 is considered a biomarker in various cancer studies, but its precise role is controversial. Previous studies have been performed mainly on breast cancer [19][20][21][22], colorectal cancer [23][24][25][26], lung cancer [27,28], and thyroid papillary carcinoma [12,13,29,30]. Many studies reported that DUSP4 showed an oncogenic effect.…”

“…Therefore, many studies on dysregulated DUSP4 expression and cancer have been performed. In several types of cancer, DUSP4 expression affects carcinogenesis and drug resistance; thus, DUSP4 is considered a candidate prognostic marker or therapeutic target [10][11][12][13]. However, its exact molecular mechanism and clinicopathologic role in cancer are unknown.…”

The Importance of miRNA in the Diagnosis and Prognosis of Papillary Thyroid Cancer

“…Its underexpression promotes PTC progression [ 54 ]. A study that was recently performed by Hu et al has found that miR-122-5p, through dual specificity phosphatase 4 (DUSP4) inhibition, suppresses PTC oncogenesis [ 55 ] ( Table 2 ).…”

Expression of SOX2OT, DANCR and TINCR long non‑coding RNAs in papillary thyroid cancer and its effects on clinicopathological features

“…On the other hand, SOX2OT contains a binding site for miR-204 and acts as a sponge for this miRNA ( 11 ). Similarly, some studies have reported that miR-132 and miR-122 have tumor suppressor roles in PTC by suppressing FOXA1 and DUSP4 expression, respectively ( 35 , 36 ). SOX2OT binds to these two miRNAs and suppresses their expression ( 11 ).…”