Down-regulated lncRNA TP73-AS1 reduces radioresistance in hepatocellular carcinoma via the PTEN/Akt signaling pathway
Authors: Wei Song
Miaomiao Sun
Jingjing Zhang
Qingxin Xia
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatocellular carcinoma; PTEN/Akt signaling pathway; apoptosis; long non-coding RNA TP73-AS1; proliferation
Affiliations: Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, PR China, Department of Cardiovascularology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, PR China

Abstract:  Objective: Recently, the role of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) has been assessed. Our research was determined to investigate the impacts of lncRNA TP73-AS1 on radioresistance of HCC by modulating PTEN/Akt signaling pathway. Methods: Expression of TP73-AS1 in HCC tissues and cells was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The HCC cells were conducted with different doses of irradiation, then the survival, colony formation and apoptosis were determined by a series of assays. The HCC cell line with a higher expression of TP73-AS1 was transfected with TP73-AS1-siRNA and X-rayed, the expression of TP73-AS1, cell survival, radiosensitivity, and apoptosis were evaluated. Subcutaneous tumorigenesis in nude mice was adopted to record the size of tumors before and after the radiation. RT-qPCR and Western blot analysis were used to clarify the activation of PTEN/Akt signaling pathway. Results: TP73-AS1 was highly expressed in HCC tissues and cells. With the increasing dose of radiation, the relative proliferation activity and survival fraction (SF) of HCC cells was gradually reduced, while the total apoptosis rate was gradually elevated. TP73-AS1 knockdown promoted radiosensitivity and apoptosis, repressed cell proliferation, making it an inhibitor of tumor in HCC. Moreover, reduced TP73-AS1 was able to decline the phosphorylation of Akt and increase the expression of PTEN in HCC. Down-regulated TP73-AS1 could repress tumorigenesis by promoting radiosensitivity in nude mice with HCC. Conclusion: Our study suggests that lncRNA TP73-AS1 was highly expressed in HCC and participated in radioresistance of HCC via PTEN/Akt signaling pathway. Abbreviations: lncRNAs: long non-coding RNAs; lncRNAs: HCC: hepatocellular carcinoma; RT-qPCR: reverse transcription quantitative polymerase chain reaction; survival fraction: SF; lncRNA TP73-AS1: LncRNA P73 antisense RNA 1T; PTEN: Phosphatase and tensin homologue; Akt: Protein kinase B; P13K: phosphatidylinositol 3-kinase; TNM: tumor, node and metastasis; ACJJ: American Joint Committee on Cancer; FBS: fetal bovine serum; EDTA: ethylene diamine tetraacetic acid; NC: negative control; DMEM: Dulbecco's modified Eagle medium; OD: optical density; PE: Plating efficiency; FITC/PI: fluoresceine isothiocyanate/propidium iodide; PBS: phosphate buffered solution; GAPDH: Glyceraldehyde phosphate dehydrogenase; ANOVA: one-way analysis of variance; LSD-t: least significant difference test. 

Retracted: No

PubPeer comments:
 Another falsified paper accepted by apparently blind peer-reviewers and an editorial office that apparently don t care. The picture speaks for it self. I am speechless.  , 
 I started to annotate the shenanigans within Fig 2c before discovering Indigofera s earlier comprehensive exegesis.  , 
 I came here to report the same concerns - only to find that both Indigofera as well as Hoya reported them already here. I can only write here that I completely agree with their findings. September 9, 2021 , 
 Dear Hoya camphorifoliauff1a I m Miaomiao sun, the corresponding author. First of all, thank you very much for questioning this article. After checking the experimental results, the first author found that there were misuses of pictures. In order to confirm the reliability of the results of this experiment, the first author repeated all experiments. I will send you the results of all repeated experiments and hope you will evaluate them again.       Thank you. Best Regards, Miaomiao sun , 
 #3 Dear Elisabeth M Bikuff1a I m Miaomiao sun, the corresponding author. First of all, thank you very much for questioning this article. After checking the experimental results, the first author found that there were misuses of pictures. In order to confirm the reliability of the results of this experiment, the first author repeated all experiments. I will send you the results of all repeated experiments and hope you will evaluate them again.       Best Regards, Miaomiao sun , 
 Dear Dr. Sun, It is always appreciated if the authors of papers reply to the concerns raised about their papers. In some cases, they can take away concerns by e.g. showing high-resolution scans of blots or cells, that clearly show there were no duplications. But you are not showing high-resolution scans, only complete new sets of images that have little resemblance to the original sets. Even of more concern, the original published images appear to contain repetitive elements. See comments #1 and #2, yellow boxes. Instead of providing new figures can you please give a satisfactory explanation for these repetitive features? They are very unexpected in flow cytometry and colony formation assays. Also, can you please provide the original uncropped blots for e.g. Figure 6b? Or the high resolution flow cytometry images for Figure 2e? ,