LncRNA TRERNA1 promotes malignant progression of NSCLC through targeting FOXL1
Authors: Y Wang
D-B Luo
H-B Lv
J-H Chu
A-L Salai
X-H Sun
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA TRERNA1; FOXL1; non-small cell lung cancer (NSCLC); regulatory effect; malignant progression
Affiliations: Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China. .

Abstract:  Objective: Previous studies have shown the carcinogenic role of long-chain non-coding RNAs (lncRNA) TRERNA1. However, the role of TRERNA1 in non-small cell lung cancer (NSCLC) has not been reported. This research aims to explore the regulatory effect of TRERNA1/FOXL1 axis on the malignant progression of NSCLC. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression levels of TRERNA1 and FOXL1 in 39 pairs of tumor tissues and paracancerous ones collected from NSCLC patients. The potential relation between TRERNA1 expression and clinical indicators of NSCLC patients was analyzed. Meanwhile, expression levels of TRERNA1 and FOXL1 in NSCLC cell lines were also detected by qRT-PCR. In addition, TRERNA1 knockdown model was constructed in H358 and SPC-A1 cells. Cell counting kit-8 (CCK-8), cell colony formation assay, and flow cytometry were applied to analyze the influence of TRERNA1 on NSCLC cell biological functions. Finally, Dual-Luciferase reporter gene assay and cell reverse recovery experiments were performed to figure out the underlying mechanisms of TRERNA1 in regulating NSCLC progression. Results: QRT-PCR results indicated that the expression level of lncRNA TRERNA1 in tumor tissue samples of NSCLC patients was remarkably higher than that in adjacent tissues. Compared with NSCLC patients with low expression of TRERNA1, patients with high TRERNA1 expression had a worse pathological stage and overall survival. Similarly, compared with cells in sh-NC group, the proliferation ability of cells in sh-TRERNA1 group was remarkably attenuated. In addition, cell ratio in the G1 phase increased after knockdown of TRERNA1, suggesting the arrested G1/S cell cycle. Subsequently, FOXL1 was downregulated in NSCLC cell lines and tumor tissues. Meanwhile, FOXL1 level was verified to be negatively correlated with TRERNA1 level. Additionally, the binding between TRERNA1 and FOXL1 was confirmed by Dual-Luciferase reporter gene assay. Cell reverse investigation indicated the involvement of FOXL1 in TRERNA1-regulated malignant progression of NSCLC. Conclusions: LncRNA TRERNA1 was up-regulated both in NSCLC tissues and cell lines. Its level was associated with pathological stage and poor prognosis in NSCLC. In addition, lncRNA TRERNA1 could promote the malignant progression of NSCLC via modulating FOXL1. 

Retracted: No

PubPeer comments:
 Fig 3E.  There was a significant negative correlation between TRERNA1 and FOXL1 expression in non-small cell lung cancer tissues . Rescaled for comparison with (right) a superimposition of 20 versions of the same correlation scatterplot from different papers. Darker data-points indicate points that are present in more versions. Below: 3E overlaid on the composite. More points in common than one would expect. ![file] , 
 Fig 1D.  Kaplan-Meier survival curve of patients with non-small cell lung cancer based on TRERNA1 expression; the prognosis of patients with high TRERNA1 expression was significantly worse than that of low expression group . ![file] Pairs of K-M plots of this form, resembling combs or walls made of Lego, are a recurring feature of a papermill. In many of the K-M plots, survival crashes precipitously at 75 months, but in a minority of them the nose-five is at 55 months, as here. Another common characteristic of the papermill s output is a Table 1 of this form, where the column heads promise to convert the numbers within each patient subgroup into percentages - a promise which remains unfulfilled. ![file] , 
 #2 Fig 1D again (at right). Paired with (left) Fig 1D from [Xu, Hou Yang (2019)] , to make the point that pairs of K-M plots of this form are more common in this journal than one would expect. ![] ,