LncRNA MEG3 suppresses migration and promotes apoptosis by sponging miR-548d-3p to modulate JAK-STAT pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a lethal malignancy and its prognosis remains dismal. Thus, a deeper understanding of the mechanisms is needed to provide a new insight for new therapies. It has been reported that long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was downregulated in OSCC tissues, however, its functional mechanism remains uncertain. Here, we found that the overexpression of MEG3 suppressed migration and promoted apoptosis in OSCC cell lines, while inhibition of MEG3 exhibited opposite effect. We also found that MEG3 could effectively sponge miR-548d-3p and decrease its expression level. Moreover, miR-548d-3p repressed the expression of SOCS5 and SOCS6 through binding their 3'UTR, thereby modulating the JAK-STAT signaling pathway and functioning as an oncogene in OSCC cells. Importantly, overexpression of MEG3 enhanced the expression of SOCS5 and SOCS6 to regulate JAK-STAT pathway, whereas miR-548d-3p overexpression decreased the effects of MEG3 on levels of SOCS5/SOCS6. Furthermore, upregulated expression of miR-548d-3p could abrogate the effect of MEG3 overexpression on migration and apoptosis in OSCC cell lines. In addition, the overexpression of MEG3 inhibited tumor migration and facilitated apoptosis in vivo. Together, our results revealed that MEG3 could modulate JAK-STAT pathway via miR-548d-3p/SOCS5/SOCS6 to suppresses migration and promote apoptosis in OSCC. Our research indexed a new functional mechanism of MEG3 in OSCC, and this mechanism may be a potential prognostic factor and therapeutic target. © 2019 IUBMB Life, 2019.

Tan J ，Xiang L ，Xu G 《-》

LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression.

Wang X ，Li H ，Shi J 《-》

Long noncoding RNA UCA1 promotes cell growth, migration, and invasion by targeting miR-143-3p in oral squamous cell carcinoma.

The long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is dysregulated in many types of tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study aims to determine the effect of lncRNA UCA1 on OSCC. Fifty-six paired OSCC and adjacent nontumorous tissues were collected and the levels of UCA1, miR-143-3p, and MYO6 in the tissues were evaluated by qRT-PCR. In in vitro experiments, cell viability, migration, and invasion were measured by, respectively, performing CCK-8, wound healing, and transwell assays. The target relationships among UCA1, miR-143-3p, and MYO6 were verified by dual-luciferase assay. Western blot and immunohistochemistry were carried out to determine the protein levels. Xenograft mouse model was established to explore the effects of UCA1 in vivo. Levels of UCA1 and MYO6 were increased significantly in OSCC, while the level of miR-143-3p was decreased compared with the adjacent nontumorous tissues. UCA1 promoted OSCC cell growth, migration, and invasion both in vitro and in vivo, while miR-143-3p reversed the progression. MYO6 was validated as a target for miR-143-3p, and MYO6 overexpression reversed the effects of miR-143-3p mimic on OSCC cells. LncRNA UCA1 contributes to the proliferation and metastasis of OSCC cells by targeting miR-143-3p and upregulating its downstream gene MYO6. UCA1 could serve as a promising novel target therapy for treatment of OSCC.

Duan Q ，Xu M ，Wu M ，Zhang X ，Gan M ，Jiang H ... -  《Cancer Medicine》

LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR-184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR-184 to repress its expression. Rescue experiments suggested that downregulation of miR-184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP-resistant OSCC cells. Moreover, UCA1 could perform as a miR-184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP-mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients.

Fang Z ，Zhao J ，Xie W ，Sun Q ，Wang H ，Qiao B ... -  《Cancer Medicine》

Low expression of lncRNA MEG3 promotes the progression of oral squamous cell carcinoma by targeting miR-21.

Zhang LL ，Hu D ，Zou LH 《-》