Effect of miR-21 on apoptosis in hepatoblastoma cell through activating ASPP2/p38 signaling pathway in vitro and in vivo
Authors: Ping Tian
Zenglian Li
Enqin Liu
Hao Xu
Lili Liu
Likun Wang
Xidong Li
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ASPP2; MiR-21; apoptosis; hepatoblastoma; p38.
Affiliations: Department of Pathology, Linyi People's Hospital, Linyi, China;, Department of Infectious Diseases, Linyi People's Hospital, Linyi, China

Abstract:  The objective of this study was to investigate the mechanism underlying miR-21-associated apoptosis in HB. In this study, HB and adjacent tissues were collected from patients with HB. RT-PCR, FISH, western blot, apoptosis assay, migration, invasion and wound healing assays, caspase activity assay, luciferase reporter assays, and xenografts mouse model were used to determine the effects of miR-21 on HB cell apoptosis. The results revealed that miR-21 was up-regulated in both HB cell and tissue and was associated with progression of HB. MiR-21 inhibitor enhanced the apoptosis level in HB cells. MiR-21 inhibitor showed reduced abilities of migration and invasion. ASPP2 was a target gene of miR-21. Inhibition of ASPP2 increased abilities of migration and invasion in HB cells. Furthermore, miR-21 inhibitor caused increased activity p-38 signaling. In a xenografts mouse model, miR-21 inhibitor could significantly suppress tumor growth in nude mice along with enhanced expressions of ASPP2 and p38. Taken together, the results suggest that upregulation of miR-21 is related to HB progression and miR-21-associated apoptosis in HB is mediated through ASPP2/p38 signaling pathway in vitro and in vivo. This study provides novel insight into the effects of miR-21 on HB apoptosis and clue to develop new therapies. 

Retracted: No

PubPeer comments:
 Figure 2E,F: a micrograph has been duplicated and presented as something else. Figure 3D,E: same issue as above. Figure 4E,F: The tumors shown in Figure 4E are much more different in size compared to the tumors shown in Figure 4F. Why? ![file] , 
 #1 *[right]* Fig 4F.  Representative tumors from mice treated with has-miR-NC or miR-21 inhibitor. *[left]* Fig 5C from [Wen et al (2021)] .  The tumor weights of different treated mice on 28 days . ![file] , 
 Also of interest: Figs 3C and 4A.  ASPP2 siRNA treatment decreased protein expression of ASPP2 in HB cells ;  Effects of miR-21 inhibitor on HB apoptosis in vivo . ![file] , 
 #2 As already noted, what appear to be the same tumors (and transformations of them) appear in three papers by unrelated groups of researchers: - **Fig 4F from [Liu et al (2019)] **. - Fig 7C from [Shi et al (2020)] . - Fig 5C from [Wen et al (2021)] . ![] ![] Here I am interested in the **ruler**, which migrated around the institutions along with the tumors. Note its distinctive markings: on the 10 , a stain at the tip of the leftward stroke of the 1 , and a stain in the middle of the righthand curve of the 0 . On the 20 , a stain along the tops of both digits. The ruler continued its travels and we find it in Fig 6A of [Ji Shang (2020)] ,  Effects of RPL38 knockdown on the size of MKN-45 xenograft tumors in nude mice. ![file] Fig 7A of [Liu et al (2020)] .  Tumors in nude mice after tumorigenesis . ![file] Figs 3C, 5E, 7F of [Wang et al (2020)] .  Tumor volume and tumor weight in mice . ![file] In Fig 4B of [Zhao et al (2020)] ,  Tumor weight was determined in the isolated tumors from the nude mice , the resolution is lower but the 20 seems to display the same stain. ![file] The same low-resolution caveat applies to Fig 8B of [Xu et al (2020)] ,  Tumor weight was increased after miR-483-3p overexpression . ![file] It would make sense if the xenograft experiments were all the work of a single laboratory, but none of the papers mention outsourcing any research to an outside agency. ,