Circular RNAs (circRNA) are a new member of endogenously produced noncoding RNAs that have been characterized as key regulators of gene expression in a variety of malignances. However, the role of circRNA in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we identified unique circRNA that regulate OSCC progression and metastasis and pave roads for future research in early diagnosis, prevention, and treatment of OSCC. Transcriptomic analyses identified a circRNA derived from IGHG locus (circIGHG) as significantly upregulated in OSCC and positively associated with poor prognosis of OSCC. circIGHG directly bound miR-142-5p and consequently elevated IGF2BP3 activity. Knockdown of circIGHG led to impaired expression of IGF2BP3 and attenuated aggressiveness of OSCC cells. Epithelial–mesenchymal transition was the main mechanism through which circIGHG/IGF2BP3 promotes metastasis of OSCC. Overall, these results demonstrate that circIGHG plays a pivotal role in OSCC development and metastasis and has potential to serve as a biomarker and therapeutic target for early-stage diagnosis and treatment of OSCC. Significance: These findings broaden our insights regarding regulation of OSCC progression by circular RNA and serve as a reference for future clinical research in OSCC diagnosis and treatment.

We aimed to detect the functions of miR‐375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR‐375 and SLC7A11 in OSCC tissues and cells were measured with RT‐qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR‐375 and SLC7A11 in CAL‐27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR‐375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR‐375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR‐375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR‐375 upregulated cells. Collective data suggested that miR‐375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR‐375 or knockout of SLC7A11 could be therapeutically exploited.

Background Human bone marrow-derived mesenchymal stem cells (HBMSCs) are characterized by multiple differentiation potential and potent self-renewal ability, yet much remains to be elucidated on what determines these properties. Long-chain noncoding RNAs (lncRNAs) have been suggested to be involved in multiple biological processes under physiological and pathological conditions, including osteogenic differentiation. Methods Alkaline phosphatase (ALP) activity assay, ALP staining, and Alizarin Red Staining were used for osteogenic potential detection. Western blot and qRT-PCR were used to examine the expression of LINC00707 and miR-370-3p. RNA-binding protein immunoprecipitation was used to detect the interaction between LINC00707 and RNA-induced silencing complex. Luciferase reporter assay was used to confirm the binding sites of miR-370-3p to LINC00707 and WNT2B. Results We demonstrated that LINC00707 expression was gradually increased in HBMSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas LINC00707 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between LINC00707 and miR-370-3p and then confirmed the direct binding sites of miR-370-3p on LINC00707. While miR-370-3p upregulation led to decreased osteogenic differentiation, LINC00707 overexpression could reverse this suppression, indicating that LINC00707 acts as a competing endogenous RNA (ceRNA) for miR-370-3p. Moreover, LINC00707 could act as a ceRNA to upregulate WNT2B via miR-370-3p inhibition. Conclusions In conclusion, our study provides a novel lncRNA-miRNA regulatory network and a promising target to modulate the osteogenic differentiation of HBMSCs. Electronic supplementary material The online version of this article (10.1186/s13287-019-1161-9) contains supplementary material, which is available to authorized users.

Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self‐renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer‐associated ncRNA transcript‐1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR‐106a‐5p and then confirmed the direct binding sites of miR‐106a‐5p on lncPCAT1. Although miR‐106a‐5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR‐106a‐5p. Moreover, lncPCAT1 could sponge miR‐106a‐5p to upregulate miR‐106a‐5p‐targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR‐106a‐5p, could bind to the promoter of lncPCAT1 and then form a feed‐forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA‐miRNA feed‐forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs.

Tongue squamous cell carcinoma (TSCC), the most common epithelial cancer identified in the oral cavity, has become one of the most common malignancies across the developing countries. Increasing evidence indicates that long non-coding RNAs (lncRNAs) serve as important regulators in cancer biology. The focally amplified long non-coding RNA in epithelial cancer (FALEC) was found downregulated in the tissues of tongue squamous cell carcinoma (TSCC) and was predicted to present a good prognosis by bioinformatics analysis. Experiments indicated that FALEC knockdown significantly increased the proliferation and migration of TSCC cells both in vitro and in vivo ; however, FALEC overexpression repressed these malignant behaviors. RNA pull-down and RNA immunoprecipitation demonstrated that FALEC could recruit enhancer of zeste homolog 2 (EZH2) at the promoter regions of extracellular matrix protein 1 (ECM1), epigenetically repressing ECM1 expression. The data revealed that FALEC acted as a tumor suppressor in TSCC and may aid in developing a novel potential therapeutic strategy against TSCC.