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 ... -  《-》

Long non-coding RNA TTN-AS1 facilitates tumorigenesis of papillary thyroid cancer through modulating the miR-153-3p/ZNRF2 axis.

Long non-coding RNAs (lncRNAs) are crucial modulators in the tumorigenesis of numerous cancers, including papillary thyroid cancer (PTC). However, it is unclear whether lncRNA TTN antisense RNA 1 (TTN-AS1) can regulate PTC progression. The present study aimed to reveal the mechanism and function of TTN-AS1 in PTC. TTN-AS1 expression in 92 pairs PTC tissues and four PTC cells was measured via a quantitative reverse transcriptase-polymerase chain reaction assay. The relationship of TTN-AS1 expression and clinical pathological features of PTC patients was analyzed using a chi-squared test. The biofunction of TTN-AS1 in PTC was identified by loss or gain-of-function assays. Based on bioinformatics analysis and mechanism experiments, the molecular mechanism of TTN-AS1 was analyzed and identified. A high level of TTN-AS1 was observed in PTC tissues and cells. The expression level of TTN-AS1 is possibly associated with lymphatic metastasis, TNM stage and the overall survival of PTC patients. Functionally, TTN-AS1 knockdown inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition in PTC, whereas overexpression of TTN-AS1 led to the opposite results. Mechanistically, TTN-AS1 acted as a competing endogenous RNA by sponging microRNA-153-3p (miR-153-3p) to elevate zinc and ring finger 2 (ZNRF2) expression. Additionally, a high level of TTN-AS1 in PTC was closely correlated with the activity of the phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway. The findings obtained in the present study indicate that TTN-AS1 facilitated PTC progression by regulating the miR-153-3p/ZNRF2 axis and activating the PI3K/Akt/mTOR pathway.

Cui Z ，Luo Z ，Lin Z ，Shi L ，Hong Y ，Yan C ... -  《-》

STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p/STAT3 axis and PI3K/AKT signalling pathway.

Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC. qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration. High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p. STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.

Wen J ，Wang H ，Dong T ，Gan P ，Fang H ，Wu S ，Li J ，Zhang Y ，Du R ，Zhu Q ... -  《-》

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》

Altered expression of DLG1-AS1 distinguished papillary thyroid carcinoma from benign thyroid nodules.

He T ，Wang H ，Sun J ，Wu J ，Gong F ，Li S ，Wang H ，Li Y ... -  《BMC Endocrine Disorders》