ABSTRACT
The article "MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK", by L.-J. Wei, D.-M. Bai, Z.-Y. Wang, B.-C. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4738-4745-DOI: 10.26355/eurrev_201906_18055-PMID: 31210300 has been retracted by the authors for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/0E5B55962B277F3D0ABBC0451DAAB3). In particular, concerns were raised about Figure 3 and Table I. Unfortunately, the authors are not able to confirm nor deny this concern as they did not find the primary data for figures. The authors decided to study this experiment again to deliver more precise results. After consultation among the authors, in line with the rigorous attitude towards scientific research, authors agreed that it was necessary to withdraw the article and make further research and improvement. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18055.
ABSTRACT
OBJECTIVE: To investigate the role of long non-coding RNA (lncRNA) CACNA1G-AS1 in regulating proliferative and invasive abilities of colorectal cancer (CRC) cells by mediating p53, thus influencing the progression of CRC. PATIENTS AND METHODS: CACNA1G-AS1 level in CRC tissues and adjacent normal tissues was first determined. Its level in CRC patients with different tumor stages was detected as well. Changes in proliferative and invasive abilities of HCT116 and SW480 cells influenced by CACNA1G-AS1 were evaluated. Subcellular distribution of CACNA1G-AS1 was analyzed. Through Western blot, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assay, the interaction between CACNA1G-AS1 and EZH2 was assessed. The biological function of the target gene of CACNA1G-AS1 was finally explored. RESULTS: CACNA1G-AS1 was upregulated in CRC tissues compared to adjacent normal ones. Its level remained higher in CRC patients with stage III-IV compared to those with stage I-II. Knockdown of CACNA1G-AS1 reduced proliferative and invasive abilities of HTC116 and SW480 cells. CACNA1G-AS1 was mainly distributed in the nucleus. Moreover, CACNA1G-AS1 was verified to interact with EZH2. Knockdown of CACNA1G-AS1 or EZH2 upregulated p53 level and decreased the recruitment ability of EZH2 on p53. Finally, p53 knockdown could partially reverse the regulatory effect of CACNA1G-AS1 on the proliferative ability of HCT116 cells. CONCLUSIONS: CACNA1G-AS1 downregulates p53 level by forming a carcinogenic complex with EZH2, thereby enhancing the proliferative and invasive abilities of CRC cells.
Subject(s)
Calcium Channels, T-Type/metabolism , Colorectal Neoplasms/metabolism , Down-Regulation , RNA, Long Noncoding/metabolism , Tumor Suppressor Protein p53/metabolism , Calcium Channels, T-Type/genetics , Cell Proliferation , Cells, Cultured , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , RNA, Long Noncoding/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
OBJECTIVE: This study aims to detect the expression pattern of microRNA-375 in colorectal cancer (CRC), and to examine its specific mechanism in regulating the progression of CRC. PATIENTS AND METHODS: We detected microRNA-375 expression in 50 pairs of CRC and paracancerous tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between microRNA-375 expression and pathological indexes of CRC patients was analyzed. Cellular expression of microRNA-375 in CRC cell lines was detected as well. Regulatory effect of microRNA-375 on biological behaviors of CRC cells was examined, including proliferative, invasive and migratory abilities. We used bioinformatics method to predict the potential target of microRNA-375 and finally explored their interactive functions in regulating CRC progression. RESULTS: MicroRNA-375 expression remained higher in CRC tissues relative to paracancerous ones. CRC patients with a high level of microRNA-375 tended to have higher rates of lymph node metastasis and distant metastasis compared with those with a low level. Transfection of microRNA-375 inhibitor greatly reduced proliferative, invasive and migratory abilities of CRC cells. RECK was predicted to be the target of microRNA-375, which was downregulated in CRC tissues and cells. Besides, RECK expression was negatively regulated by microRNA-375 in CRC. Rescue experiments confirmed that microRNA-375/RECK axis promoted the malignant progression of CRC. CONCLUSIONS: MicroRNA-375 is upregulated in CRC, and correlated to lymph node metastasis and distant metastasis. MicroRNA-375 enhances invasive and migratory abilities of CRC cells via regulating RECK.
Subject(s)
Colorectal Neoplasms/metabolism , GPI-Linked Proteins/metabolism , MicroRNAs/metabolism , Aged , Cell Movement , Cell Proliferation , Cells, Cultured , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , GPI-Linked Proteins/genetics , Gene Expression Profiling , Humans , Male , MicroRNAs/genetics , Middle Aged , Signal Transduction/geneticsABSTRACT
Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.
Subject(s)
Carcinoma, Hepatocellular/prevention & control , DNA-Activated Protein Kinase/metabolism , Diet/adverse effects , Fructose-Bisphosphate Aldolase/metabolism , Gene Expression Regulation, Neoplastic , Liver Neoplasms/prevention & control , Nuclear Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis , Biomarkers, Tumor , Caloric Restriction , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement , Cell Proliferation , DNA-Activated Protein Kinase/genetics , Female , Fructose-Bisphosphate Aldolase/genetics , Humans , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Nuclear Proteins/genetics , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics , Xenograft Model Antitumor AssaysABSTRACT
Neuronal Toll-like receptors (TLRs)-2 and -4 have been shown to play a pivotal role in ischemic brain injury, and the interleukin-1 receptor associated kinases (IRAKs) are considered to be the key signaling molecules involved downstream of TLRs. Here, we investigated the expression levels of IRAK-1 and -4 and the effects of IRAK-1/4 inhibition on brain ischemic insult and neuronal hypoxia-induced injury. Male Sprague-Dawley (SD) rats and the rat neuroblastoma B35 cell line were used in these experiments. Permanent middle cerebral artery occlusion (MCAO) was induced by the intraluminal filament technique, and B35 cells were stimulated with the hypoxia-mimetic, cobalt chloride (CoCl(2)). Following induction of hypoxia/ischemia (H/I), B35 cells and cerebral cortical neurons expressed higher levels of IRAK-1 and -4. Furthermore, IRAK-1/4 inhibition decreased the mortality rate, functional deficits, and ischemic infarct volume by 7 days after MCAO. Similarly, IRAK-1/4 inhibition attenuated CoCl(2)-induced cytotoxicity and apoptosis in B35 cells in vitro. Our results show that IRAK-1/4 inhibition decreased the nuclear translocation of the nuclear factor-kappaB (NF-κB) p65 subunit, the levels of activated (phosphorylated) c-jun N-terminal kinase (JNK) and cleaved caspase-3, and the secretion of TNF-α and IL-6 in B35 cells at 6 h after CoCl(2) treatment. These data suggest that IRAK-1/4 inhibition plays a neuroprotective role in H/I-induced brain injury.
