RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1.

This study aimed to explore the role of miR-429 on the progression of oral squamous cell carcinoma (OSCC). OSCC cell lines were transfected with miR-429 mimic, pcDNA3.1-RUNX1, or pcDNA3.1-ITGB1, and their cell viability, apoptosis, migration, and invasion abilities were analyzed by cell counting, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, wound healing, and transwell assays, respectively. Furthermore, luciferase reporter assay, RNA pull-down, and ChIP were used to assess the regulation of miR-429, RUNX1, and ITGB1 expression in OSCC. Lastly, the biological role of the RUNX1/miR-429 feedback loop was explored in nude mice. The results revealed that miR-429 level was down-regulated, while RUNX1 and ITGB1 levels were up-regulated in OSCC tissues and that miR-429 was negatively correlated with RUNX1 and ITGB1 in OSCC tissues. Transfection of miR-429 mimic suppressed OSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, we found that miR-429 participated in OSCC progression by directly targeting ITGB1. Additionally, we found that RUNX1 negatively regulated miR-429 expression by binding to its promoter. Our results also revealed that the RUNX1/miR-429 feedback loop regulated ITGB1 expression and that RUNX1 overexpression rescued the inhibitory effects of miR-429 mimic on OSCC cells. In addition, miR-429 mimic significantly suppressed tumor growth, inflammatory cell infiltration, EMT, and ITGB1 expression in vivo, which were inhibited by RUNX1 overexpression. Altogether, these results indicate that the RUNX1/miR-429 feedback loop promoted growth, metastasis, and EMT in OSCC by targeting ITGB1.

Lu X ，Yang Y ，Chen J ，Zhao T ，Zhao X ... -  《-》

[Effects of LncRNA SNHG20 on epithelial mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells through targeted regulation of the miR-520c-3p/RAB22A pathway].

Ma M ，Chao X ，Zhao Y ，Zhao G ... -  《-》

MiR-155-5p promotes oral cancer progression by targeting chromatin remodeling gene ARID2.

Dysregulation of miRNAs is associated with aberrant migration and invasion by suppressing relevant target genes in multiple cancers, including oral squamous cell carcinoma (OSCC). Accumulating evidence suggests that microRNA-155-5p is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-155-5p in OSCC remain unclear. This study aimed to investigate the function of miR-155-5p and the molecular mechanisms underlying the influencing progression of OSCC. The miR-155-5p expression level in the OSCC tissues and oral cancer cell lines were determined by the qRT-PCR. Gain-of-function and knockdown approach were used to examine the effect of miR-155-5p on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of OSCC. The luciferase reporter assay was applied to confirm the AT-rich interactive domain 2 (ARID2) as a potential target of miR-155-5p, and the rescue experiment was employed to verify the roles of the miRNA-155-5p-ARID2 axis in OSCC progression. Immunohistochemical staining was used to detect ARID2 expression in another cohort sample tissues from OSCC patients. MiR-155-5p was significantly upregulated in OSCC tissues and cell lines. The miR-155-5p expression level was positively correlated with tumor size, TNM stage, histological grade and lymph node metastasis of OSCC patients. Functional assays demonstrated that miR-155-5p enhanced OSCC cell proliferation, migration and invasion. Mechanistically, ARID2 was identified as a direct target and functional effector of miR-155-5p in OSCC. Furthermore, ARID2 overexpression could rescue the aberrant biological function by overexpressed miR-155-5p in OSCC cells. Notably, we showed that ARID2 could be used as an independent prognosis factor in OSCC. Our results suggest that miR-155-5p facilitates tumor progression of OSCC by targeting ARID2, and miR-155-5p-ARID2 axis may be a potential therapeutic target of OSCC.

Wu M ，Duan Q ，Liu X ，Zhang P ，Fu Y ，Zhang Z ，Liu L ，Cheng J ，Jiang H ... -  《-》

LncRNA PVT1 promotes malignant progression by regulating the miR-7-5p/CDKL1 axis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), one of the most common types of head and neck squamous cell carcinoma (HNSCC), is characterized by high incidence and mortality. PVT1 is a long non-coding RNA (lncRNA) that plays an oncogenic role in various cancer types. This study aims to reveal the role and underlying molecular mechanism of PVT1 in OSCC progression. The expression levels of PVT1, miR-7-5p, and CDKL1 mRNA were evaluated using qRT-PCR. Western blot and IHC analysis were conducted to determine the protein expression of CDKL1. The biological functions of PVT1, miR-7-5p, and CDKL1 in OSCC were investigated through CCK-8, transwell migration and invasion assays. In vivo experiments utilized a xenograft model to examine the impact of PVT1 on OSCC. Furthermore, the interaction among PVT1, miR-7-5p, and CDKL1 was explored using RNA pull down assay and luciferase reporter assays. We found that PVT1 enhanced cell proliferation, migration, and invasion by targeting CDKL1. In addition, PVT1 functions as a sponge to modulate miR-7-5p, thereby influencing the expression of CDKL1 and the progression of OSCC. In conclusion, this study illustrates that the "PVT1/miR-7-5p/CDKL1" pathway is capable of promoting the progression of OSCC and may serve as a promising target for developing treatment strategies for OSCC.

Li J ，Ding S ，Li M ，Zou B ，Chu M ，Gu G ，Chen C ，Liu YJ ，Zheng K ，Meng Z ... -  《-》

The miR-1269a/PCDHGA9/CXCR4/β-catenin pathway promotes colorectal cancer invasion and metastasis.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This research focuses on investigating the impact and underlying molecular mechanisms of protocadherin gamma subfamily A, 9 (PCDHGA9) on the invasion and metastasis of CRC, aiming to identify more precise molecular markers for the diagnosis and prognosis of CRC. PCDHGA9 expression was detected using quantitative real-time quantitative polymerase chain reaction (RT-qPCR) in 63 pairs of colorectal cancer tissues. Differential gene expression from high-throughput sequencing was analyzed using ingenuity pathway analysis (IPA) to explore the biological functions of PCDHGA9 and its potential regulated genes. Bioinformatics tools were employed to explore potential upstream regulatory microRNAs of PCDHGA9. Dual-luciferase assays were performed to demonstrate the regulation between PCDHGA9 and miR-1269a. Protein mass spectrometry suggested an interaction between PCDHGA9 and HOXA1. JASPAR predicted that HOXA1 may act as a transcription factor of CXCR4. Coimmunoprecipitation, dual-luciferase assays, and nuclear-cytoplasmic fractionation experiments confirmed the molecular mechanism involving PCDHGA9, CXCR4, HOXA1, and β-catenin. Transwell, wound healing, and western blot assays were conducted to confirm the impact of PCDHGA9, miR-1269a, and CXCR4 on the invasion, metastasis, and epithelial-mesenchymal transition (EMT) functions of CRC cells in in vitro experiments. A whole-body fluorescence imaging system was used to evaluate the combined impact of miR-1269a and PCDHGA9 on the invasion and metastasis of CRC in in vivo experiments. The expression of PCDHGA9 was found to be lower in CRC tissues compared with their corresponding adjacent tissues. Low expression of PCDHGA9 potentially correlated with worse prognosis and increased chances of invasion and metastasis in CRC. miR-1269a was highly expressed in CRC tissues and acted as a negative regulator for PCDHGA9, promoting invasion, migration, and EMT of CRC cells. PCDHGA9's interaction with HOXA1 downregulated CXCR4, a transcription factor, leading to accumulation of β-catenin and further promoting invasion, migration, and EMT of CRC cells. PCDHGA9, acting as a tumor suppressor, is downregulated by miR-1269a. The low level of PCDHGA9 activates the Wnt/β-catenin pathway by releasing its interaction with HOXA1, promoting the expression of CXCR4, and causing invasion, migration, and EMT in CRC.

Mei H ，Luo Q ，Weng J ，Hao J ，Cai J ，Zhou R ，Bian C ，Ye Y ，Luo S ，Wen Y ... -  《-》