MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway
Authors: Zi-Wen Long
Jiang-Hong Wu
Ye Zhou
Cai-Hong
Ya-Nong Wang
Journal: Molecules and Cells (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PI3K/Akt signaling pathway; PTEN; apoptosis; gastrointestinal stromal tumor; microRNA-374b
Affiliations: Department of Surgery, Shigatse People's Hospital, Shigatse 857000, P.R. China., Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China., Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.

Abstract:  Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR-374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment. 

Retracted: No

PubPeer comments:
 Fig. 4A.  High protein levels of PI3K and Akt, and low protein level of PTEN in GIST tissues by Western blotting. (A) Protein band graphs and results of PTEN, PI3K and Akt protein levels in GIST tissues and adjacent normal tissues . Fig. 7C.  MiR-374b promotes GIST cell viability. ... (C) Protein levels of ki67 and PCNA by Western blotting . A loading control band appears to be reused.  Other versions appear in papers by other authors (along with many other of the WB blobs in the present paper). For instance, 9A from [Wu et al (2018a) and 5C from [Wu et al (2018)] .  , 
 Figs 4E  Protein band graphs and results of PTEN, PI3K and Akt protein expressions in GIST tissues with different pathological stage ; 8C  Protein levels of caspase-9 and bax by Western blotting ; and 10D  Protein levels of MMP2 and MMP9 by Western blotting . These are versatile WBs.  , 
 Fig 8A.  8. MiR-374b inhibits GIST cell apoptosis. (A) Results of GIST cell apoptosis in each group by flow cytometry.  The presence of a single central group of cells within each of these  raspberry infundibula *[The Shamen, 1989]* leaves me unconvinced that they really resulted from separate experimental sessions. , 
 Fig 10B.  (B) Results of cell invasion in each group by transwell assay .  I am not convinced that the Blank and NC images came from different experiments. , 
 #2 #3 #4 #1 Thank you pointed out.I checked the records right away. , 
 #2 Figs 4E, 8C, 10D again.  Here comparing 8C with [at right] 5B from [An et al (2018)] .  The protein expressions of BLNK, IL-6, IL-1u03b2, TNF-u03b1, pBTK, pPLC-u03b32, nuclear and cytosolic NF-u03baB p105 p50 and cytosolic pIu03baBu03b1 in each group after cell transfection. ... B, Protein expressions of BLNK, IL-6, IL-1u03b2, TNF-u03b1, pBTK and pPLC-u03b32.  , 
 Fig 6B.  miR-374b promotes the expressions of PI3K, and Akt and inhibits the expression of PTEN. ... (B) Protein levels of PTEN, PI3K and Akt by western blotting  Cyan rectangle marks a similar triad of blobs in Fig 5 of [Ao et al (2018)] .  Protein expression of the PI3K-Akt signaling pathway-related proteins in BGC-823 cells .  , 
 #5  Thank you pointed out.I checked the records right away. Can you tell us about the results of your check? , 
 Is it also possible to check Fig 9A?  These curves are wobbly; they overhang. They make no sense as flow-cytometry cell-cycle results, where each panel should contain a reconstructed profile that matches the raw data as closely as possible, which is not the case here. ,