MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met
Authors: Peng Liu
Jie Lin
Yue Zhao
Zhongshi Xie
Journal: American journal of translational research (2017)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MiR-144-3p; apoptosis; c-MET; multiple myeloma; proliferation.
Affiliations: Department of Vascular Surgery, The China Japan Union Hospital of Jilin UniversityChangchun 130033, China., Department of Gastrointestinal Colorectal and Anal Surgery, The China Japan Union Hospital of Jilin UniversityChangchun 130033, China., Department of Orthopaedics, The China Japan Union Hospital of Jilin UniversityChangchun 130033, China.

Abstract:  MicroRNA-144-3p (miR-144-3p) has been implicated in the development of many types of cancer. However, its role in multiple myeloma (MM) remains largely unknown. In this study, we found that miR-144-3p was downregulated in both MM cell lines and plasma from patients with MM. In vitro studies further showed that transfection of an miR-144-3p mimic into MM cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and apoptosis. In addition, we found that miR-144-3p could directly target the 3'-untranslated region of cellular-mesenchymal to epithelial transition factor (c-MET) and suppress c-MET expression and its downstream signaling pathway (PI3K/AKT). Rescue experiments revealed that overexpression of c-MET partially reversed the inhibition effect of miR-144-3p in MM cells. In vivo studies confirmed that restoration of miR-144-3p suppressed tumor growth in xenograft nude mice by repressing c-MET. Overall, these findings demonstrate that miR-144-3p functions as a tumor suppressor in MM by targeting c-MET, suggesting that miR-144-3p might serve as a potential therapeutic target in MM. 

Retracted: No

PubPeer comments:
 *[right]* Fig 2E.  Cell ... apoptosis ... assessed in MM1S cells transfected with miR-144-3p mimic or miR-NC . *[left]* Fig 2D from [Li et al (2016)] .  Cell ... apoptosis ... determined in SW480 cells after transfected with miR-152 mimic or miR-NC . ![file] , 
 *[left]* FIg 3F.  c-MET expression at the ... protein level was determined by ... western blot analysis of four MM cell lines and plasma from normal individuals . *[right]* Fig 5 from [Pan et al (2015)] .  Effect of co-expression of pSi-STAT3-LKB1 plasmid on relevant tumor effector molecules in vitro. SKOV3 cells were transfected with different recombinant treatment plasmids. Non-transfection was used as a negative control. At 48 h after transfection, the cells were collected and protein levels of p21, p-p53, cyclin D1, survivin and Bcl-2 were analyzed by western blotting using specific antibodies . ![file] Unexpected similarities. , 
 Clockwise from upper left: - Fig 2D from [Pang et al (2015)] .  cell cycle progression ... determined in HepG2 cells transfected with the miR-154 mimic or miR-NC. - Fig 2D from [**Zhao et al (2017)**] .  cell cycle stage ... assessed in MM1S cells transfected with miR-144-3p mimic or miR-NC. - Fig 2D from [Li et al (2016)] .  The cell cycle procession was detected by flow cytometry after transfection with miR-494 or miR-NC . - Fig 2C from [Luan et al (2015)] .  Cell cycle was measured in glioma cells at posttransfection by flow cytometry . ![file] The same panels keep appearing. --------------------------------- *[left]* Fig 2A from [Liu et al (2015)] .  Effect of DOX and Ad sh-NOB1 alone or in combination on cell cycle of TPC-1 cells. (A) Cell DNA content distribution in each phase . *[upper right]* Fig 2C from [Song et al (2015)] .  Determination of HeLa cell cycle distribution by PI staining after transfection with miR-133a or miR-Ctrl . *[lower right]* Fig 2d from [Zhang et al (2015)] .  The cell cycle was detected by PI staining after being transfected with miR-133a or miR-NC. ![file] The same panels keep appearing. --------------------------------------------------- Clockwise from top left: - Fig 3A from [Liu et al (2015)] .  Effects of miR-222 inhibitor on HepG2 cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015)] .  Effects of microRNA-145 (miR-145) on multiple myeloma (MM) cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Li et al (2015)] .  Enforced expression of miR-338-3p induced cell cycle distribution and cell apoptosis in EC9706 cells. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015b)] ,  miR-137 induces changes in cell cycle distribution and cell apoptosis in SKOV3 cells. (A) Cell DNA content distribution in each phase ![file] The same panels keep appearing. ----------------------------------------------------- Fig 2D from [Zhou et al (2016)] .  Cell cycle distribution of U2OS cells transfected with the miR-154 mimic was determined by flow cytometry . ![file] ,