H19 promotes the migration and invasion of colon cancer by sponging miR-138 to upregulate the expression of HMGA1
Authors: Xuan Chen
Jianjun He
Qingqiang Yang
Xin Wang
Chunyan Tang
Journal: International Journal of Oncology (2017)
Discipline: CLINICAL MEDICINE
Keywords: Colon cancer; Long non-coding RNA H19; miR-138; HMGA1; Migration
Affiliations: Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China., Department of Nursing, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Abstract:  Colon cancer is the most common digestive system malignancy, along with high mortality rate, familial transmissibility and hepatic metastasis. Our study investigated the role of long non-coding RNA H19 in colon cancer. We found that H19 was overexpressed in colon cancer tissues and cell lines, the interference of H19 by short hairpin RNA (shRNA) effectively decreased the migration and invasion of colon cancer cells (HT-29 and RKO). Besides, miR-138 was predicted a target of H19, and low expression of miR-138 was found in colon cancer tissues and cells. The silence of H19 strongly increased the expression of miR-138. The decreased level of miR-138 was elevated adding miR-138 mimic in RKO cells transfected with lncRNA-H19. Similarly, the upregulated level of miR-138 was downregulated adding miR-138 inhibitor in RKO cells transfected with H19 shRNA. The luciferase reporter confirmed the targeting reaction between H19 and miR-138. Moreover, the high-mobility group A (HMGA1) protein was predicted as a target of miR-138. HMGA1 was suppressed by H19 shRNA and could be up-regulated by miR-138 inhibitor. The migration and invasion ability of colon cancer was restrained by H19 shRNA and promoted by miR-138 inhibitor. Finally, the in vivo experiment revealed that H19 shRNA strongly reduced the tumor growth and tumor volume. H19 shRNA also inhibited metastasis via suppressing hepatic metastases and the expression of metastasis-related proteins. Taken together, our research indicated an H19-miR138-HMGA1 pathway in regulating the migration and invasion of colon cancer, providing new insight for treatment of colon cancer. 

Retracted: Yes

PubPeer comments:
  Figure 5. H19 enhances tumor growth and metastasis in vivo. RKO-H19 shRNA cells and RKO-H19 scramble cells were injected into BALB c nude mice. (A) Representative tumors from two groups are shown .  For comparison, Fig 7A of [Zhang et al (2017)] .  The lower rows (treated tumors) appear to be the same. Upper rows show the same tumors in the two left-hand positions. , 
 Fig 4H.  Invasive [RKO] cells are shown through Transwell invasion assay .  For comparison, Fig 6A from [Zhang et al (2017)] ,  miR-135a offsets the role of UCA1 on cell migration and invasion. SW1990 cells were transfected with UCA1 siRNA and or miR-135a inhibitor or mock, respectively. (A) The Transwell invasion assay was conducted to observe the invasive cells in SW1990 cells .  , 
 At left, Fig 5G.  (G) Production of migration markers ...VEGF in formalin-fixed, paraffin-embedded tumors from ... RKO-H19 scramble mice was detected through IHC analysis . At right, Fig 7G from [Li et al (2018)] .  immunohistochemistry analysis of MMP-14 in the tumor tissues.  Despite different descriptions and lack of links between teams of researchers, images overlap. , 
 Please be noted, the same or very similar crease of Surgical pad are showing on the following 11 chinese papers. Also, the samples on the pad are somehow shared in those papers. UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer bySponging miR-135a. Oncology research (2017) . DOI: 10.3727 096504017x14888987683152.  H19 promotes the migration and invasion of colon cancer by spongingmiR-138 to upregulate the expression of HMGA1. INTERNATIONAL JOURNAL OF ONCOLOGY (2017). DOI: 10.3892 ijo.2017.3941.  Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells In Vitroand In Vivo via Targeting miR-203. Oncology research (2018). DOI: 10.3727 096504017x14965095236521.  Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancervia Targeting miR-198 and Promoting the MAPK1 Pathway. Oncology research (2018) . DOI: 10.3727 096504017x14944585873631.  HOTAIR contributes to cell proliferation and metastasis of cervical cancer via targetting MAPK1 axis. Bioscience reports (2018). DOI: 10.1042 bsr20171563.  Long non-coding RNA MEG3 inhibits cell growth of gliomas by targeting miR-93 andinactivating PI3K AKT pathway. Oncology reports (2017). DOI: 10.3892 or.2017.5871.  The inhibitory effect of MEG3 miR-214 AIFM2 axis on the growth of T-cell lymphoblastic lymphoma. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4006.  Inhibition of BAMBI reduces the viability and motility of colon cancervia activating TGFu2011u03b2 Smad pathway in vitro and in vivo. ONCOLOGY LETTERS. 10.3892 ol.2017.6811.  HNF1Au2011AS1 promotes growth and metastasis of esophageal squamous cellcarcinoma by sponging miRu2011214 to upregulate the expression of SOX-4. INTERNATIONAL JOURNAL OF ONCOLOGY. DOI: 10.3892 ijo.2017.4034.  Astragaloside IV inhibits progression of glioma via blocking MAPK ERKsignaling pathway. Biochemical and Biophysical Research Communications (2017). DOI: 10.1016 j.bbrc.2017.07.052.  Epigenetic silence of HOTAIR contributes to the metastasis of pancreaticcancer via targeting miR-138. Oncology Research (2017). DOI: 10.3727 096504017X15138544374391.  Possibly the following one: Long Noncoding RNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting miR-184. Oncology research (2018) . DOI: 10.3727 096504017x14980882803151  , 
 A scatterplot based on the same points is used in Fig 5E of [Li et al (2018)] , Fig 6D of [Zhang et al (2017)] , Fig 1C of [Chen et al (2019)] , Fig 3K of [Yang et al (2017)] , Fig 7A of [Fan et al (2017)] and Fig 5H of [Wang et al (2017)] .  This deserves some sort of award. , 
 Retracted [6 April 2021] .  Following the publication of this paper, it was drawn to our attention by an interested reader that a row of tumour images featured in Fig. 5A of the above paper were strikingly similar to those featured in Fig. 7A of an article appearing in *Oncology Research* [Zhang X, Gao F, Zhou L, Wang H, Shi G and Tan X: UCA1 regulates the growth and metastasis of pancreatic cancer by sponging miR-135a. Oncol Res 25: 1529-1541, 2017]. Furthermore, similarities in the data were also identified comparing Fig. 4A in the above paper with Fig. 6A in the same paper published in *Oncology Research* by Zhang et al. Finally, immunohistochemistry data featured in Fig. 5G were strikingly similar to data featured in Fig. 7G in the following article [Li Y, Luo H, Xiao N, Duan J Wang Z and Wang S: Long noncoding RNA SChLAP1 accelerates the proliferation and metastasis of prostate cancer via targeting miR-198 and promoting the MAPK1 pathway. Oncol Res 26: 131-143, 2018].  The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, although the authors never responded within a reasonable time to confirm that the paper should be retracted. The Editor has therefore made the executive decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. ,