Long non-coding RNA titin-antisense RNA1 contributes to growth and metastasis of cholangiocarcinoma by suppressing microRNA-513a-5p to upregulate stratifin

Abstract

Cholangiocarcinoma (CCA) is one of the most common histological types of primary hepatic malignancy and is associated with poor overall prognosis, causing a ponderous burden on human life. Hence, it is necessary to elucidate the pathogenesis of CCA. The objective of our research was to shed light on the mechanism through which long non-coding RNA titin-antisense RNA1 (lncRNA TTN-AS1) is involved in the development of CCA. Reverse transcription quantitative polymerase chain reaction was used to detect TTN-AS1 expression in CCA samples and cells. Functional experiments were performed using the Cell Counting Kit-8, 5-ethynyl-2ʹ-deoxyuridine, transwell, and in vivo tumor growth assays. The relationship between TTN-AS1, miR-513a-5p, and stratifin (SFN) was explored using a dual luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Pearson correlation analysis. The result showed that TTN-AS1 and SFN are highly expressed in CCA tissues. Bioinformatics analysis, luciferase reporter and RIP experiments revealed the correlation between TTN-AS1, miR-513a-5p, and SFN. In addition, silencing TTN-AS1 mitigated CCA cell proliferation and migration. Mechanistically, miR-513a-5p is sponged by TTN-AS1. The miR-513a-5p inhibitor abolished the effect of TTN-AS1 silencing on the aggressive behaviors of CCA cells. Furthermore, we showed that miR-513a-5p is a regulator of CCA by targeting SFN. TTN-AS1 induced CCA cell growth and metastasis via the miR-513a-5p/SFN pathway, which offers a new strategy for therapeutic interventions for CCA.

Circulating tumor cell-derived exosome–transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells

“…LncRNA MT1JP is downregulated in cholangiocarcinoma tissues, and its expression is associated with TNM staging and lymph node metastasis [ 36 ]. LncRNA TTN-AS1 is highly expressed in cholangiocarcinoma tissues [ 37 ]. Moreover, exosomal delivery of TTN-AS1 derived from gastric cancer cells can promote gastric cancer progression [ 38 ].…”

Circular RNA Sec61 subunit alpha isoform 1 by competitive absorption of microRNA‐513a‐5p mediates peroxisomal biogenesis factor 5 expression and promotes the malignant phenotype of non‐small cell lung cancer

“…miR-513a-5p is a well-documented tumor suppressor gene in different cancer types, such as cholangiocarcinoma, 31 liver cancer, 32 and clear cell renal cell carcinoma. 33 We noticed that miR-513a-5p was underexpressed in NSCLC cells, and exogenous miR-513a-5p expression was able to rescue malignant behaviors of NSCLC cells caused by circSEC61A1 overexpression.…”

Long intergenic non-protein-coding RNA 467 promotes tumor progression and angiogenesis via the microRNA-128-3p/vascular endothelial growth factor C axis in colorectal cancer

“…qRT-PCR was used to detect nuclear and cytosolic RNA levels with U6 and β-actin, respectively. GAPDH was used as the cytoplasmic reference, and U6 was used as the nuclear reference [ 35 , 36 ].…”

“…Forty-eight hours after transfection, the fluorescent reporter protein was detected. Finally, the dual-luciferase reporter assay (Promega, Madison, WI, USA) was used to evaluate luciferase activity by measuring the absorbance on a microplate reader, according to the manufacturer’s instructions [ 36 ].…”