<p>Inhibition of microRNA-15b-5p Attenuates the Progression of Oral Squamous Cell Carcinoma via Modulating the <em>PTPN4</em>/STAT3 Axis</p>

Abstract

Background Emerging evidence has demonstrated the important functions of microRNAs (miRNAs) in human malignancies. This study focuses on the function of miR-15b-5p on the oral squamous cell carcinoma (OSCC) progression and the molecules involved. Methods Tumor and the paracancerous tissues were obtained from OSCC patients. Differentially expressed miRNAs between the tumor and normal tissues were screened out. miR-15b-5p expression in tumors and acquired cells was determined, and its correlation with patient survival was analyzed. Knockdown of miR-15b-5p was introduced in SCC-4 and CAL-27 cells to explore its role in cell growth and metastasis. Binding relationship between miR-15b-5p and PTPN4 was validated, and altered expression of PTPN4 was introduced in cells to explore its function in OSCC development. Xenograft tumors were induced in nude mice for in vivo experiments. Results miR-15b-5p was abundantly expressed in OSCC tumors and cells and linked to poor survival in patients. Silencing of miR-15b-5p suppressed proliferation, migration, and invasion and triggered apoptosis in SCC-4 and CAL-27 cells. miR-15b-5p targeted PTPN4 . Further silencing of PTPN4 blocked the inhibiting functions of miR-15b-5p inhibitor in OSCC cell growth. The in vitro results were reproduced in vivo, where inhibition of miR-15b-5p led to a decline in tumor growth and metastasis in nude mice. PTPN4 was found as a negative mediator of the STAT3 pathway. Conclusion This study evidenced that miR-15b-5p possibly promotes OSCC development through binding to PTPN4 and the following STAT3 signaling activation. miR-15b-5p may be a potential therapeutic target for OSCC.

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

“…This study should, in the future, be expanded to other validated targets of miR-15b-5p and SFN. For instance, miR-15b-5p affects LATS2 [78], PTPN4/STAT3 [79], HPSE2 [80], axin2 [81] and RECK [32] in human cancers. On the other hand, SFN down-regulates CDK4/CDK6, inhibits tubulin polymerization [82], inhibits STAT3/HIF-1alpha/VEGF signaling [83], induces ERK1/2 and caspase-3 [51] and targets NRF2 [84] and other transcriptions factors [85].…”

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma

“…It was reported that PTPN4 was a signaling molecule of several important pathways, including signal transducer and activator of transcription 3 (STAT3), toll like receptor 4 (TLR4), mitogen-activated protein kinase 1 (MAPK1), etc. [31][32][33][34]. TFCP2L1 is a transcription regulating factor and is reported to play key roles in inflammation by regulating KLF transcription factor 4 (KLF4)/ ras homolog family member F (RHOF)/NF-κB pathway [35].…”

Specific Plasma MicroRNA Signatures in Predicting and Confirming Crohn's Disease Recurrence: Role and Pathogenic Implications

“…CREB5 expression was significantly higher in active CD than in inactive CD ( 59 ), which agrees with our in silico analysis in patients with recurrent CD. All these referred pathways have been summarized up in a supplementary Table 3 (see Supplementary Digital Content 3, http://links.lww.com/CTG/A706 ) ( 35 , 36 , 39 – 42 , 44 – 46 , 48 , 60 – 65 ).…”