Long non‐coding RNA LINC00607 silencing exerts antioncogenic effects on thyroid cancer through the CASP9 Promoter methylation
Authors: Zhongcheng Gao
Hongyan Shen
Peiyou Ren
Lei Zhao
Lanzhen Li
Journal: Journal of Cellular and Molecular Medicine (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CASP9; Long non-coding LINC00607; apoptosis; drug-resistance; methylation
Affiliations: Department of General Surgery Three Wards Linyi People’s Hospital  Linyi China, Department of Breast Surgery Linyi People’s Hospital  Linyi China

Abstract:  Thyroid cancer (TC) was the most frequent thyroid malignant tumour, accounting for about 1% of all malignant tumours. Some long non-coding RNAs (lncRNAs) have been reported to exert essential tumour promotion effects, while caspase-9 (CASP9) gene could play a promotive role in the cell apoptosis in TC. However, whether they have a specific effect on TC remains unclear. Hence, this study aims to explore the relationship between LINC00607 and CASP9, and its effect in TC. LINC00607 expression in the TC tissues and cell lines was determined. Then, we explored the combination effect between a LINC00607 and a methylation inhibitor 5-Aza-dc in doxorubicin-resistant ARO cells using colony formation assay, flow cytometry, WST-1 and EdU assay, as well as in vivo tumour growth assay. Besides, the dual-luciferase reporter gene assay, RIP, ChIP, methylation-specific PCR and BSP method were employed to detect the relationship between LINC00607 and CASP9 and its methylation. LINC00607 expression was up-regulated in the doxorubicin-resistant TC cell lines and tissues and negatively correlated to the poor prognosis of TC patients. Knockdown of LINC00607 suppressed doxorubicin resistance, proliferation and colony formation, and promoted cell apoptosis of TC cells in vitro, as well as suppressed tumour growth in vivo, whereas LINC00607 overexpression was observed to exercise the opposite effects. Notably, it was also revealed that LINC00607 down-regulated the CASP9 expression by promoting CASP9 promoter methylation. In conclusion, LINC00607 could inhibit the apoptosis and augment the doxorubicin resistance of TC cells by decreasing CASP9 expression, which might provide a novel therapeutic target for TC treatment. 

Retracted: No

PubPeer comments:
  From a period between **September 2016 and September 2017**, 47 specimens were harvested from patients who underwent thyroid surgery at the Institutional Review Board of Linyi Peopleu2019s Hospital. All patients were diagnosed as TC by pathological examination and were treated with doxorubicin. The collected specimens were classified into 2 categories as resistance (n = 18) and sensitive (n = 29) and both were refrigerated at -80u2103. In the study, the clinical data and follow-up data (**60 months**) of the patients, excluding those who died of other ailments or accidents, were provided.  60 months of follow-up data requires that patients were followed through to the period **September 2021 to September 2022**. For a paper that was submitted on 29 February 2020, revised on 4 December 2020. How does this work? , 
 Fig 7B,  representative images of tumours . ![file] Fig 6B from [Li et al (2021a)] .  Representative images of dissected tumours from nude mice and tumour weight from different groups . ![file] The authors are from unrelated institutions. Is it possible that part of the present research was conducted by a third-party laboratory? ![file] , 
 A third sighting of this peripatetic ruler! Fig 7c from [Jia et al (2021)] ,  Representative images of transplanted tumors in tumor-bearing nude mice, n = 15 . ![] UPDATE Two more sightings from Figs 3i, 5h of [Zhou et al (2020)] .  Representative macroscopic image of a xenograft tumor after treatment with oe-circ_002117 or oe-NC ;  Representative xenograft tumor pictures upon treatment with miR-370 mimic, miR-370 inhibitor or controls . ![] Fig 6A of [Xin et al (2021)] , Fig 6A.  Representative macroscopic images of xenograft tumor formation in nude mice . ![] -------------------- UPDATE: Fig 8B of [Wang et al (2021)] . ![] , 
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