MiR‐143‐3p suppresses cell proliferation, migration, and invasion by targeting Melanoma‐Associated Antigen A9 in laryngeal squamous cell carcinoma

Abstract

Previously we found that melanoma‐associated antigen‐A9 (MAGE‐A9) was a significantly upregulated biomarker in laryngeal squamous cell carcinoma (LSCC). A high expression of MAGE‐A9 indicates an unfavorable survival outcome, and the MAGE‐A9 expression level is an independent prognostic factor of LSCC. To explore the mechanism of MAGE‐A9 upregulation, several predicted regulatory microRNAs were screened and validated in LSCC cells. In the current study, we found that miR‐143‐3p (MAGE‐A9 related miRNAs) expression levels correlated negatively with the MAGE‐A9 protein expression in LSCC tissues. Dual‐luciferase reporter assays and Western blot analysis revealed MAGE‐A9 to be a direct target of miR‐143‐3p. Furthermore, a series of in vitro gain‐ and loss‐of‐function assays revealed that miR‐143‐3p inhibited LSCC cell proliferation, migration, and invasion. Also, miR‐143‐3p suppressed LSCC tumorigenesis in vivo. These effects were clinically relevant, as a lower expression of miR‐143‐3p occurred in severer clinical stages and represented poor overall survival in patients with LSCC. Taken together, these results suggest that downregulation of miR‐143‐3p contributes to tumor progression through upregulation of MAGE‐A9. The expression level of these two key molecules maintained LSCC progression, thus, highlighting the potential of miR‐143‐3p as a therapeutic target for human LSCC.

Involvement of Dual Strands of miR-143 (miR-143-5p and miR-143-3p) and Their Target Oncogenes in the Molecular Pathogenesis of Lung Adenocarcinoma

“…Several miRNAs exist in close proximity on the human genome (defined as miRNA clusters). The expression levels of miRNAs within miRNA clusters are controlled by the same molecular mechanisms [25]. In the human chromosome 5q32 region, pre- miR-143 and pre- miR-145 form the miRNA cluster, and their promoter regions contain p53 binding sites, resulting in p53-dependent expression [26].…”

miR‑375‑3p inhibits the progression of laryngeal squamous cell carcinoma by targeting hepatocyte nuclear factor‑1β

“…The prognosis and treatment of LSCC have improved with advancements in therapeutic strategies; the 5-year overall survival rate of patients with LSCC is ~64% ( 5 ). Increasing evidence suggest that miRNAs exert tumor suppressive or oncogenic functions in the progression of LSCC ( 21 , 40 – 42 ). A previous study reported that miR-375-3p is downregulated in head and neck cancer ( 24 ).…”

“…Aberrant expression of miRNAs has been reported in LSCC, and is associated with angiogenesis, tumor growth and metastasis ( 18 – 20 ). For example, miR-143-3p suppresses the proliferation and invasion of LSCC cells by targeting melanoma-associated antigen A9 ( 21 ). A recent study demonstrated that miR-154 inhibits the progression of LSCC by regulating N-acetylgalactosaminyltransferase 7 (GALNT7) ( 22 ).…”

Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma

“…Overexpression of miR-613 reduces LSCC cell proliferation, invasion, and blocks G1/S phase transition by targeting the PDK1 gene [13]. Furthermore, miR-1297, miR-143-3p, miR-503 and miR-205 also promote LSCC cell progression [14][15][16][17]. Recent studies have confirmed that miR-17-5p plays critical roles in tumor progression, such as pancreatic cancer, breast cancer, hepatocellular carcinoma, gastric cancer and prostate cancer [18][19][20][21][22].…”