The lncRNA HOXA11-AS acts as a tumor promoter in breast cancer through regulation of the miR-125a-5p/TMPRSS4 axis.

Long non-coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11-AS functions in the progression of breast cancer (BC). HOXA11-AS and miR-125a-5p levels were measured by a quantitative real-time polymerase chain reaction, whereas western blotting determined TMPRSS4 levels in BC tumor tissues, adjacent normal tissues and BC cell lines. The roles of HOXA11-AS, miR-125a-5p and TMPRSS4 in BC proliferation were investigated using cell counting kit-8, colony formation and flow cytometry assays, whereas scratch and transwell assays were used to measure metastasis. RNA pull-down assays and dual-luciferase assays assessed direct interactions between HOXA11-AS and miR-125a-5p. The effects of HOXA11-AS in vivo were investigated in a BC xenograft model. HOXA11-AS was upregulated in tumor tissues of 56 BC patients compared to adjacent non-tumor tissues, with high levels being associated with worse overall survival. Silencing of HOXA11-AS inhibited the proliferation and metastasis of BC cells, leading to cell cycle arrest in G0/G1 and induction of apoptosis. We identified miR-125a-5p as a target of HOXA11-AS, with miR-125a-5p inhibitors partially restoring the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. We also determined that miR-125a-5p targeted TMPRSS4 mRNA, with HOXA11-AS knockdown and miR-125a-5p mimics suppressing TMPRSS4. Overexpression of TMPRSS4 partially compensated for the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. Finally, we confirmed the mechanism of HOXA11-AS in the regulation of tumorigenesis in the mouse model. HOXA11-AS regulates the tumorigenic ability of BC via the miR-125a-5p/TMPRSS4 axis. This provides insights for regulatory mechanisms involved in BC progression, and may enable new treatment strategies in the clinical setting.

Xu Y ，Ren Z ，Wang X ，Ren M ... -  《-》

Long noncoding HOXA11-AS knockdown suppresses the progression of non-small cell lung cancer by regulating miR-3619-5p/SALL4 axis.

Accumulating evidence suggested that many long noncoding RNAs (lncRNAs) were widely involved in the development and progression of non-small cell lung cancer (NSCLC). However, the roles of lncRNA homeobox A11 antisense (HOXA11-AS) and its underlying mechanism in NSCLC remains largely unknown. The expression levels of HOXA11-AS, miR-3619-5p and sal-like protein 4 (SALL4) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was used to measure the protein levels of hexokinase II (HK2) and SALL4. Cell proliferation, apoptosis, migration and invasion were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell assay, respectively. The glucose consumption and lactate production were measured using glucose assay kit and lactate assay kit, respectively. The potential binding sites between miR-3619-5p and HOXA11-AS or SALL4 were predicted by online software and verified by luciferase report assay. A xenograft tumor model was established to confirm the function of HOXA11-AS in NSCLC in vivo. HOXA11-AS and SALL4 were upregulated while miR-3619-5p was downregulated in NSCLC tissues and cells. HOXA11-AS knockdown suppressed cell proliferation, migration, invasion, and glycolysis but promoted apoptosis in NSCLC cells. Moreover, miR-3619-5p could directly bind to HOXA11-AS and its inhibition attenuated the inhibitory effect of HOXA11-AS knockdown on progression of NSCLC cells. Furthermore, SALL4 was a direct target of miR-3619-5p and its overexpression reversed the anti-tumor role of miR-3619-5p in NSCLC cells. Besides, HOXA11-AS modulated SALL4 expression via sponging miR-3619-5p. Additionally, silencing HOXA11-AS inhibited tumor growth though upregulating miR-3619-5p and downregulating SALL4. Collectively, HOXA11-AS knockdown inhibited the progression of NSCLC by regulating miR-3619-5p/SALL4 axis, which might offer a novel avenue for interpreting the mechanism of NSCLC development.

Xia H ，Niu Q ，Ding Y ，Zhang Z ，Yuan J ，Jin W ... -  《-》

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression.

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.

Yan L ，Li K ，Feng Z ，Zhang Y ，Han R ，Ma J ，Zhang J ，Wu X ，Liu H ，Jiang Y ，Zhang Y ，Zhu Y ... -  《-》

The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2.

Xu CH ，Xiao LM ，Liu Y ，Chen LK ，Zheng SY ，Zeng EM ，Li DH ... -  《-》

LncRNA HOXA11-AS promotes OSCC progression by sponging miR-98-5p to upregulate YBX2 expression.

Oral squamous cell carcinoma (OSCC) is a type of oral malignancy. Long non-coding RNAs (lncRNAs) have been shown to be related to the occurrence and development of many cancers. Here, we aimed to study the role and molecular mechanism of lncRNA Homeobox A11 antisense RNA (HOXA11-AS) in OSCC. The expression levels of HOXA11-AS, miR-98-5p and Y box binding protein 2 (YBX2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), flow cytometry and transwell assays were utilized to determine the proliferation, apoptosis, migration and invasion of OSCC cells. Western blot (WB) analysis was conducted to measure the levels of apoptosis, epithelial-mesenchymal transition (EMT), proliferation-related proteins and YBX2 protein. Besides, Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays were carried out to examine the relationship among HOXA11-AS, miR-98-5p and YBX2. The mice xenograft models were constructed to further determine the effect of HOXA11-AS on OSCC tumor growth in vivo. HOXA11-AS was highly expressed in OSCC tissues and cells. Knockdown of HOXA11-AS significantly reduced proliferation, migration, invasion and EMT, while promoted apoptosis of OSCC cells. MiR-98-5p was a target of HOXA11-AS, and its inhibitor could revert the inhibition effect of silenced-HOXA11-AS on the progression of OSCC. Also, YBX2 was a target of miR-98-5p, and its overexpression could invert the suppression effect of miR-98-5p overexpression on the progression of OSCC. YBX2 expression was regulated by HOXA11-AS and miR-98-5p. Furthermore, HOXA11-AS silencing could reduce the tumor growth of OSCC in vivo. HOXA11-AS plays an active role in the progression of OSCC, and the discovery of HOXA11-AS/miR-98-5p/YBX2 axis provides new therapeutic targets for OSCC.

Niu X ，Yang B ，Liu F ，Fang Q ... -  《-》