This study aims to investigate the effect of miR-21-5p on process of colon adenocarcinoma (COAD) cells and its connection with neural cell adhesion molecule L1 (CHL1).
Different expressions of mRNAs ...and miRNAs were calculated with microarray analysis. QRT-PCR and western blot were performed to quantify miR-21-5p and CHL1 expression. Flow Cytometry, MTT assay, colony formation assay, transwell assay and ELISA were performed to evaluate propagation and invasiveness of COAD cells. Dual luciferase reporter assay was employed to scrutinize the relationship between miR-21-5P and CHL1. We performed in vivo experiment to detect the impact of miR-21-5p and CHL1 on COAD tumor growth.
Expression level of miR-21-5p increased in both COAD tissues and cells. MTT and Cell cycle assay showed that overexpression of miR-21-5p accelerated proliferation of COAD cells. Transwell assay indicated that miR-21-5p promoted cell invasion. The result of dual luciferase reporter assay indicated that miR-21-5p targeted CHL1 directly and inhibited its expression. The result of in vivo experiments showed that down-regulation of miR-21-5p decreased the volume and weight of tumor, while knockdown of CHLI stimulated tumor growth.
The overexpression of miR-21-5p can promote propagation and invasiveness of COAD cells through inhibiting the expression of CHL1.
We established an iPSC line (TSHSUi001-A) from a patient with Peutz-Jeghers syndrome, carrying heterozygous c.290 + 1G > A mutation in STK11 gene. Peripheral blood mononuclear cells were reprogrammed ...using non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL and c-MYC. The iPSC line expressed pluripotency markers, could differentiate into cells of three germ layers in vitro, and displayed a normal karyotype.
Long non-coding RNA (lncRNA) has been implicated in various types of human cancer. However, the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in gastric cancer ...remains unclear. In the present study, MALAT1 expression was significantly upregulated in gastric tumors compared with adjacent healthy tissue in patients with gastric cancer. Furthermore, MALAT1 plasma expression was higher in patients with gastric cancer compared with healthy controls and was found to have prognostic and diagnostic value independent of patients' lifestyle choices. Cell proliferation assay and Transwell migration and invasion results indicated that the overexpression of MALAT1 resulted in increased proliferation, migration and invasion of gastric cancer cells
, possibly through activation of the phosphoinositide 3-kinase/protein kinase B pathway.
Circular RNAs (circRNAs) are a new class of noncoding RNAs, play a crucial role in tumor initiation and development. Hsa_circ_0001546 is a novel circular RNA that was downregulated in gastric cancer ...(GC) tissues, however its function and mechanism in GC has not been studied. Our study verified that circ_0001546 was decreased in GC and correlated with the poor prognosis. Next, Pull-down assay and dual-luciferase reporter assay verified that miR-421 was a target of circ_0001546 while ATM (Ataxia telangiectasia mutated) was target by miR-421. Overexpression of circ_0001546 inhibited the proliferation and chemoresistance of HGC-27 cells, and increased the expression of ATM. In addition, circ_0001546 overexpression reversed the effect of miR-421 overexpression. What is more, circ_0001546 inhibits the chemoresistance of HGC-27 cells to L-OPH (Oxaliplatin) may through the activation of the ATM/checkpoint kinase 2 (Chk2)/p53-dependent signaling pathway. In summary, our study proved that circ_0001546 sponges miR-421 to upregulate the expression level of ATM and inhibit the proliferation and chemoresistance through the activation of the ATM/Chk2/p53-dependent pathway.
Display omitted
•Hsa_circ_0001546 is declined in gastric cancer and correlated with the poor prognosis.•Hsa_circ_0001546 inhibits the proliferation and chemoresistance of HGC-27 cells.•Circ_0001546 competes with ATM to absorb miR-421 and increased the expression of ATM.•Hsa_circ_0001546 inhibit drug resistance via the ATM/Chk2/p53-dependent pathway.
•This study explores the role of MBNL1-AS1 in colon cancer via miR-412-3p and MYL9.•MBNL1-AS1 and MYL9 is downregulated in colon cancer.•MBNL1-AS1 acts as a sponge of miR-412-3p and negatively ...regulates miR-412-3p.•MBNL1-AS1 mediates colon cancer stem cell properties by sponging miR-412-3p.•This study provides a promising therapeutic strategy for colon cancer treatment.
Colon cancer is a common cancer that is a threat to human health. Some long non-coding RNAs (lncRNAs) have been observed to exert roles in colon cancer. Here, the current study is aimed to explore the potential mechanism of lncRNA MBNL1 antisense RNA 1 (MBNL1-AS1) in progression of colon cancer and the associated mechanisms.
Microarray analysis was performed to screen differentially expressed lncRNA and genes associated with colon cancer and its potential mechanism. The functional role of MBNL1-AS1 in colon cancer was analyzed, followed identification of the interaction among MBNL1-AS1, microRNA-412-3p (miR-412-3p), and MYL9. Subsequently, CSC viability, migration, invasion, and apoptosis were detected though a series of in vitro experiments. At last, in vivo experiments were performed to assess tumor formation of colon CSCs.
MBNL1-AS1 and MYL9 were poorly expressed in colon cancer. MBNL1-AS1 could competitively bind to miR-412-3p so as to promote MYL9 expression. Enhancement of MBNL1-AS1 or inhibition of miR-412-3p was shown to decrease CSC proliferation, migration, and invasion but promote apoptosis. Moreover, MBNL1-AS1 reversed the CSC-like properties as well as xenograft tumor formation in vivo induced by miR-412-3p.
Collectively, the present study suggests an inhibitory role of MBNL1-AS1 in colon cancer by upregulating miR-412-3p-targeted MYL9. Thus, this study provides an enhanced understanding of MBNL1-AS1 along with miR-412-3p and MYL9 as therapeutic targets for colon cancer.
Aerobic glycolysis metabolic reprogramming is one of the most important hallmarks of malignant tumors. Increasing evidence indicates that long non‐coding RNAs (lncRNAs) are able to regulate ...glycolysis metabolic reprogramming and promote cancer progression by functioning as competing endogenous RNAs. lncARSR is a newly identified onco‐lncRNA in renal cancer, but its potential role in metastatic colorectal cancer (CRC) remains unclear. Here, we analyzed specimens from 89 patients with CRC and demonstrated that lncARSR was highly expressed in CRC tissues and negatively associated with survival. Positron emission tomography‐computed tomography imaging with fluoro‐2‐d‐deoxyglucose F18 to evaluate glucose uptake showed that lncARSR expression was positively correlated with maximum standardized uptake values. Functionally, ectopic expression of lncARSR promoted the invasion, metastasis, and glycolysis metabolic reprogramming of CRC cells in vitro and in vivo, while these activities were inhibited by silencing lncARSR expression. Molecularly, lncARSR sponged miR‐34a‐5p and further mediated hexokinase 1 (HK1)‐related aerobic glycolysis in vitro and in vivo. Clinically, high lncARSR and HK1 expression predicted poor survival of patients with CRC, especially when combined with low miR‐34a‐5p expression. Collectively, we identified lncARSR as an onco‐lncRNA in CRC and demonstrated that the combination of lncARSR/miR‐34a‐5p/HK1 may be a potential prognostic biomarker of CRC.
Here, we demonstrated that lncARSR was high expression in CRC tissues and negatively associated with survival. lncARSR as a onco‐lncRNA, combination of lncARSR/miR‐34a‐5p/HK1 may be a potential prognostic biomarker of CRC.
Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated ...that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model. And palmitic acid (PA) treatment increased the miR-181b expression while decreased SIRT1 expression in HepG2 cells. Further, we identified that SIRT1 is a direct downstream target of miR-181b. Ectopic expression of miR-181b significantly repressed the 3′-UTR reporter activities of SIRT1 in a dose-dependent manner, while the effect of miR-181b was interrupted when the binding site of miR-181b within the SIRT1 3′-UTR was mutated. And overexpression of miR-181b reduced both the mRNA and protein levels of SIRT1 in HepG2 cells. We also found that inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo. And the effect of miR-181b on steatosis was blocked by SIRT1 overexpression. Taken together, our data indicated that increased expression of miR-181b potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target SIRT1.
•MiR-181b was increased while SIRT1 was decreased in both human NAFLD patients and HFD-fed mice.•SIRT1 is a direct target gene of miR-181b.•Inhibition of miR-181b expression alleviates hepatic steatosis both in vitro and in vivo.•overexpression of SIRT1 blocked the effect of 181b on hepatic steatosis.
The current study aimed to investigate the relationship between the severity of gastroesophageal reflux disease (GERD) according to the Los Angeles (LA) classification and esophageal motility using ...high-resolution manometry (HRM) and 24-hour esophageal pH monitoring.We examined 124 patients with GERD from January 2016 to June 2018. The LA classification of each patient was determined by endoscopy. HRM was performed by the intraluminal water infusion method. HRM and 24-hour esophageal pH monitoring parameters of the patients were studied and statistically compared.On HRM examination, GERD symptoms were found to be associated with worsened distal contractile integral (DCI), ineffective esophageal motility (IEM), peristalsis break (PB), lower esophageal sphincter (LES) pressure, and the 4-second integrated relaxation pressure (IRP4s) of LES pressure along with the grade of LA classification, especially in patients having grade C and D GERD who had transverse mucosal breaks. The 24-hour pH monitoring study revealed that patients classified as having grade C or D GERD had an esophageal pH < 4.0 for a longer time than those with grade O, A, or B GERD. Similar results were found regarding the duration of the longest reflux event, the number of reflux episodes longer than 5 minutes, and the number of reflux episodes. Patients with higher grade esophagitis had higher De Meester scores, which suggested greater esophageal acid exposure. Hiatal hernia (HH) was more closely related to LES pressure, IRP4s, and acid exposure, whereas DCI, IEM, and PB were not statistically different between patients with GERD with and without HH.Patients with severe esophagitis may have motor dysfunction not only in the LES but also in the esophageal body, with resulting increased esophageal acid exposure, which causes esophagitis. Low LES pressure might be the main reason that patients with HH develop esophagitis. GERD without HH may be due to a variety of motor dysfunctions.
Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives and natural products and biologically active compounds. The classic method of synthesizing chiral ...propargylamines involves the asymmetric alkynylation of imines. Here, we report a significant advance in the catalytic asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn-selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide syn-configured propargylamines with two adjacent stereogenic centres and a transition metal-free organocatalytic asymmetric approach to β-alkynyl-β-amino acids with high efficiency and practicality, via a chiral Brønsted base-catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with α-substituted β-keto esters and less-acidic malonate (thio)esters as nucleophiles, respectively. A catalytic activation strategy is also disclosed, which may have broad implications for use in catalysis and synthesis.
PDF
