RETRACTED ARTICLE: microRNA -140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5
Authors: Mei Wang
Lianhong Li
Shujun Fan
Lu Wang
Lihui Yu
Wenyue Zhao
Xiaocui Han
Jiazhi Li
Jie Shen
Jianwu Tang
Bo Song
Ying Lu
Jun Mao
Bo Wang
Journal: Stem Cell Research & Therapy (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ADAMTS5; Colorectal cancer; IGFBP5; Invasion; Metastasis
Affiliations: Department of Pathology, Dalian Medical University, Dalian, 116044, People's Republic of China., Teaching Laboratory of Morphology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian, 116044, People's Republic of China., Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian, 116044, People's Republic of China., Key Laboratory of Tumor Metastasis Research of Liaoning Province, Dalian Medical University, Dalian, 116044, People's Republic of China., Department of Pathology, Dalian Medical University, Dalian, 116044, People's Republic of China. ., Teaching Laboratory of Morphology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian, 116044, People's Republic of China. .

Abstract:  Background: Colorectal cancer (CRC) is one of the most common malignancies in the world. microRNA-140-5p (miR-140) has been shown to be involved in cartilage development and osteoarthritis (OA) pathogenesis. Some contradictions still exist concerning the role of miR-140 in tumor progression and metastasis, and the underlying mechanism is uncertain. Methods: Immunohistochemistry was performed to determine the expressions of ADAMTS5 and IGFBP5 in CRC tissues. Human CRC cell lines HCT116 and RKO were transfected with miR-140 mimic, inhibitor, or small interfering RNA (siRNA) against ADAMTS5 or IGFBP5, respectively, using oligofectamine or lipofectamine 2000. Scratch-wound assay and transwell migration and invasion assays were used to evaluate the effects of miR-140 on the capabilities of migration and invasion. The levels of miR-140 and ADAMTS5 and IGFBP5 mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to examine the expression of ADAMTS5 and IGFBP5 proteins. Results: miR-140 was significantly reduced, whereas ADAMTS5 and IGFBP5 were upregulated, in the human CRC tissues compared to the corresponding normal colorectal mucosa. miR-140 downregulation and ADAMTS5 or IGFBP5 overexpression were associated with the advanced TNM stage and distant metastasis of CRC. There was a reverse correlation between miR-140 levels and ADAMTS5 and IGFBP5 expression in CRC tissues. ADAMTS5 and IGFBP5 were downregulated by miR-140 at both the protein and mRNA levels in the CRC cell lines. The gain-of- and loss-of-function studies showed that miR-140 inhibited CRC cell migratory and invasive capacities at least partially via downregulating the expression of ADAMTS5 and IGFBP5. Conclusions: These findings suggest that miR-140 suppresses CRC progression and metastasis, possibly through downregulating ADAMTS5 and IGFBP5. miR-140 might be a potential therapeutic candidate for the treatment of CRC. 

Retracted: Yes

PubPeer comments:
 Figure 3 b c e f multiple potential duplications. Some with vertical or horizontal flips and or adjustment of the scale.  , 
 I missed one potential duplication and this one involved rotation + flip + resizing, marked dark red on the right side. With so much effort that the authors might have put to polish their images, it is only fair that the journal should be notified.  , 
 Fig 3 again, concentrating on HCT116 panels.  This time marked up for comparison with Fig 2 from [Li et al (2018)] .  Labels on the panels are not compatible. , 
 #2 I have taken the liberty of complicating the diagram with a few more colors and rectangles. - In the HCT116 panels of (e), the two at the far right overlap at the edges. - Another cyan rectangle, for the Anti-NC HCT116 panel of (f), connecting it to the other cyan-rectangled AND the yellow-rectangled panels. - Navy-blue rectangles link the Anti-miR-140 HCT116 panels of (e) and (e). - The NC RKO panel from (c) belongs with the duplicated panels grouped in the lower-right margins, but after a 48-deg rotation. In fact the Control RKO panel from (e) fits into that group as well, but I have added a separate illustration for that. - The miR-140 RKO panel from (c) and the Anti-NC RKO panel from (f) (marked with scarlet rectangles) overlap after a horizontal flip and a rotation - shown in far lower right corner.   , 
 Fig 4b.  ADAMTS5 and IGFBP5 are inversely correlated with the expression of miR-140 and positively correlated with the tumor stage and metastasis of CRC. ... b Correlation of ADAMTS5 and IGFBP5 and miR-140 expression was analyzed by Spearman correlation test in CRC tissues.  There seems to be little relationship between the tissues miR-140 values in the left- and right-hand panels, as plotted on the horizontal axis. I recolored the points in the latter and superimposed them on the former, to dramatize the lack of counterparts - the horizontal-axis values are different distributions. Am I missing something?  Blue lines marks one pair of miR-140 values that DO match. , 
 #5 I also find Figure 4 interesting. Per figure caption, Figure 4b was  Correlation of ADAMTS5 and IGFBP5 and miR-140 expression ... in CRC tissues . In this way, one would expect the Y values of 60 data points in the scattered plots in b correspond to the box plots of tumor (CRC) data in a. But, I have hard time to corroborate these two plots between a and b. It would be very helpful to address this concern if the authors can provide their raw data of ADAMTS5 and IGFBP5 expression (miR-140 expression data are not absolutely necessary but would be helpful) of the 60 samples of CRC tissue.  , 
 #6 It is difficult to see how the median and quartile values shown in 4a could have emerged from the distributions shown in 4b (let alone the maximal and minimal values)  , 
 Retracted [15 February 2021] .  The authors have retracted this article because there appear to be irregularities in panels b, c, e and f in Fig. 3. The authors are repeating their experiments and will submit a new manuscript for peer review. All authors agree with this retraction. ,