LncRNA MBNL1-AS1 represses cell proliferation and enhances cell apoptosis via targeting miR-135a-5p/PHLPP2/FOXO1 axis in bladder cancer.

LncRNAs have been shown to play essential roles in bladder cancer (BC) progress. Our microarrays of clinical samples firstly screened that lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with MBNL1-AS1 in BC patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1-AS1 in the proliferation and apoptosis of BC cells in vitro and in vivo. Furthermore, miR-135a-5p (miR-135a)/PHLPP2/FOXO1 axis was focused to explore its regulatory mechanism in BC. The results showed that MBNL1-AS1 was significantly downregulated in bladder tumor tissues, and associated with BC progression. In vitro, MBNL1-AS1 knockdown increased the number of viable cells and bromodeoxyuridine-positive cells, accelerated cell cycle, and dysregulated proliferative regulators (Ki67, p21, p27, and Cyclin D1) in BC cells. The apoptotic cells and the cleavages of caspase-3/9 were reduced in MBNL1-AS1-silenced BC cells. Overexpression of MBNL1-AS1 had opposite effects on BC cell proliferation and apoptosis. Moreover miR-135a was demonstrated to interact with MBNL1-AS1, and inhibiting miR-135a reversed the effects of shMBNL1-AS1 on BC cells. The downstream effectors (PHLPP2 and FOXO1) were positively regulated by MBNL1-AS1, but negatively regulated by miR-135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that MBNL1-AS1 acts as a tumor suppressor of BC by targeting miR-135a/PHLPP2/FOXO1 axis, providing a novel insight for BC diagnosis and treatment.

Wei X ，Yang X ，Wang B ，Yang Y ，Fang Z ，Yi C ，Shi L ，Song D ... -  《Cancer Medicine》

Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer.

Mao XP ，Zhang LS ，Huang B ，Zhou SY ，Liao J ，Chen LW ，Qiu SP ，Chen JX ... -  《Journal of Translational Medicine》

Down-regulation of MBNL1-AS1 contributes to tumorigenesis of NSCLC via sponging miR-135a-5p.

Lung cancer remains a big threat to human health. Growing evidence has reported the crucial regulatory effect of lncRNAs on NSCLC progression. Nevertheless, the detailed function of lncRNA MBNL1-AS1 involved in NSCLC development is poorly known. In our research, we confirmed that MBNL1-AS1 was significantly reduced in NSCLC patient tissues and NSCLC cells. Meanwhile, we reported that overexpression of MBNL1-AS1 obviously repressed A549 and H1975 cell proliferation, blocked cell cycle and inhibited the migration and invasion. Moreover, A549 and H1975 cell apoptosis was increased by the overexpression of MBNL1-AS1. Then, we predicted that miR-135a-5p was a potential target of MBNL1-AS1 and its level was correlated with MBNL1-AS1 in NSCLC negatively. Our previous study indicated miR-135a-5p could induce lung cancer progression through regulating LOXL4. Here, we found that MBNL1-AS1 was able to regulate miR-135a-5p expression negatively. The direct binding association between MBNL1-AS1 and miR-135a-5p was proved using dual-luciferase reporter assay and RIP experiment. Subcutaneous xenotransplanted tumor model was set up and it was confirmed increased MBNL1-AS1 remarkably restrained tumorigenic ability of NSCLC through sponging miR-135a-5p in vivo. To sum up, our data revealed the significance of the MBNL1-AS1 and miR-135a-5p in NSCLC. In conclusion, MBNL1-AS1 could be a new therapeutic target to treat NSCLC.

Cao G ，Tan B ，Wei S ，Shen W ，Wang X ，Chu Y ，Rong T ，Gao C ... -  《-》

Long non-coding RNA ASMTL-AS1 inhibits tumor growth and glycolysis by regulating the miR-93-3p/miR-660/FOXO1 axis in papillary thyroid carcinoma.

Long non-coding RNA (lncRNA) is emerging as an essential player in cancer progression. However, its biological function and clinical implication in papillary thyroid carcinoma (PTC) remain poorly understood. In the current study, we found that a novel lncRNA, ASMTL antisense RNA 1 (ASMTL-AS1), was significantly downregulated in PTC. And its downregulation was positively linked to larger tumor size, advanced clinical stage and unfavorable outcome. Overexpression of ASMTL-AS1 evidently inhibited PTC cell proliferation and glycolysis, while knockdown of ASMTL-AS1 resulted in the opposite effect. Regarding the mechanism, ASMTL-AS1 was capable of sponging miR-93-3p and miR-660 to elevate FOXO1 expression, leading to repressing glycolysis and tumorigenesis. In turn, FOXO1 could also increase ASMTL-AS1 expression via directly binding to ASMTL-AS1 promoter, which formed a positive feedback regulation loop. Importantly, the regulatory axis of ASMTL-AS1/miR-93-3p/miR-660/FOXO1 was also identified in vivo. Collectively, our data clearly indicate that ASMTL-AS1 functions as a novel tumor suppressor in PTC through regulation of miR-93-3p/miR-660/FOXO1 pathway. Targeting ASMTL-AS1 and its downstream pathway may be an effective therapeutic approach for patients with PTC.

Feng Z ，Chen R ，Huang N ，Luo C ... -  《-》

LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation, migration, and invasion of bladder cancer cells.

Tang C ，Wu Y ，Wang X ，Chen K ，Tang Z ，Guo X ... -  《Human Cell》