<Emphasis Type="Italic">microRNA-145</Emphasis> modulates epithelial-mesenchymal transition and suppresses proliferation,migration and invasion by targeting <Emphasis Type="Italic">SIP1</Emphasis> in human cervical cancer cells

Purpose

Previously, it has been reported that microRNA-145 (miR-145) is lowly expressed in human cervical cancers and that its putative tumour suppressive role may be attributed to epithelial-mesenchymal transition (EMT) regulation. Here, we aimed to assess whether miR-145 may affect EMT-associated markers/genes and suppress cervical cancer growth and motility, and to provide a mechanistic basis for these phenomena.

Methods

The identification of the SMAD-interacting protein 1 (SIP1) mRNA as putative miR-145 target was investigated using a 3’ untranslated region (3’UTR) luciferase assay and Western blotting, respectively. The functional effects of exogenous miR-145 expression, miR-145 suppression or siRNA-mediated SIP1 expression down-regulation in cervical cancer-derived C33A and SiHa cells were analysed using Western blotting, BrdU incorporation (proliferation), transwell migration and invasion assays. In addition, the expression levels of miR-145 and SIP1 were determined in primary human cervical cancer and non-cancer tissue samples using qRT-PCR.

Results

We found that miR-145 binds to the wild-type 3’UTR of SIP1, but not to its mutant counterpart, and that, through this binding, miR-145 can effectively down-regulate SIP1 expression. In addition, we found that exogenous miR-145 expression or siRNA-mediated down-regulation of SIP1 expression attenuates the proliferation, migration and invasion of C33A and SiHa cells and alters the expression of the EMT-associated markers CDH1, VIM and SNAI1, whereas inhibition of endogenous miR-145 expression elicited the opposite effects. The expression of miR-145 in cervical cancer tissue samples was found to be low, while that of SIP1 was found to be high compared to non-cancerous cervical tissues. An inverse expression correlation between the two was substantiated through the anlaysis of data deposited in the TCGA database.

Conclusion

Our data indicate that low miR-145 expression levels in conjunction with elevated SIP1 expression levels may contribute to cervical cancer development. MiR-145-mediated regulation of SIP1 provides a novel mechanistic basis for its tumour suppressive mode of action in human cervical cancer cells.

     

Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186

Neurofascin (NF) is a neural cell adhesion molecule in the L1-family containing six Ig domains and multiple fibronectin type III (FnIII) repeats in its extracellular region. NF has many splicing variants and two of these are exemplars that have different cellular patterns of expression during development. NF186, which is expressed on neurons, contains an unusual mucin-like region and NF155, which is expressed on glia, contains a unique FnIII repeat with an RGD motif. Analysis of Fc fusion proteins representing different extracellular regions of NF indicate that NF186 inhibits cell adhesion and neurite outgrowth, and the inhibition is associated with the region containing the mucin-like domain. NF155 promotes neural cell adhesion and neurite outgrowth, and the RGD motif in its third FnIII repeat is critical for cell spreading and neurite outgrowth. The results suggest that different splicing variants of NF expressed on neurons and glia play distinct roles during neural development.     

Acute Renal Failure due to Cast Nephropathy in Nonsecretory Myeloma: A Case Report and Review of the Literature

Multiple myeloma is characterized by marrow plamacytsois, M spike in serum or urine electrophoresis and skeletal lytic lesions. The M spike may be absent in rare instances. We describe a case of myeloma cast nephropathy with acute renal failure who did not exhibit an M spike. λ-chain staining was documented on immunoperoxidase, suggesting paraprotein-related tubular damage.     

Secondary conversion of the Gore Excluder to operative abdominal aortic aneurysm repair

OBJECTIVE: Reports continue to document the occurrence of major adverse events after endovascular aortic aneurysm repair. Although many of these problems can be successfully managed through endovascular salvage, operative conversion with explantation of the endoprosthesis remains necessary in some patients. We report herein a review of all patients initially enrolled in multicenter US clinical trials of the Excluder endograft who underwent secondary conversion to open surgical repair. METHODS: Clinical data and relevant medical records of patients enrolled in phase I and II multicenter US clinical trials of the Excluder endograft were retrospectively reviewed for adverse events and further narrowed to those patients who underwent secondary operative conversion. Hospital records, operative and anesthesia reports, and all imaging studies were analyzed at initial implantation and at the time of subsequent open surgical repair. RESULTS: Late open conversion was performed in 16 (2.7%) of the 594 patients enrolled in the Excluder clinical trials. Presumed endotension accounted for 8 of 16 of secondary conversions. In two of these patients, however, an endoleak was identified at the time of open surgical repair. Of the remaining eight patients, two underwent conversion for device infection, five for persistent endoleak, and one for aneurysm rupture. The overall 30-day mortality was 6.25% (1/16), with one death occurring in a patient with a ruptured aneurysm. Of patients who underwent conversion because of endotension, the maximal abdominal aortic aneurysm diameter (mean +/- SD) at the time of initial implantation and subsequent graft removal was 61 +/- 11 mm and 70 +/- 10 mm, respectively. The mean time to open conversion for treatment of endotension was 37 +/- 12 months (range, 20-50 months; median, 42 months). Freedom from conversion was 98.6% and 96.7% at 24 and 48 months, respectively. CONCLUSIONS: Endotension in the absence of a demonstrable endoleak has been a major indication for late surgical conversion in patients treated with the Excluder endograft. Given the potential presence of an undetected endoleak and the possible effects of progressive sac enlargement on long-term device stability, continued close surveillance of patients with assumed endotension is required. Should changes in device design eliminate endotension, a further reduction in the already low incidence of late open conversion of the Excluder endograft can be anticipated.     

Rapidly progressive renal failure in type 2 diabetes in the tropical environment: a clinico-pathological study

BACKGROUND: Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. METHODS: Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. RESULTS: A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine >4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. CONCLUSIONS: About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

A survey of current myocardial protection practices during coronary artery bypass grafting

OBJECTIVE: To identify current myocardial protection strategies for coronary artery bypass grafting (CABG) across the UK and Ireland. METHODS: A questionnaire survey of 15 questions was sent to practising cardiac surgeons between June and October 2002. The list of surgeons was obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland database and they were contacted by postal and electronic mail. RESULTS: 118 (73.7%) out of 160 surgeons responded to the survey. 61 (51.7%) perform CABG on-pump (ONCAB) while 10 (8.5%) practice off-pump CABG (OPCAB). 47 (39.8%) perform either depending on individual cases. Of the 108 surgeons performing ONCAB, 91 (84.3%) use cardioplegia while 17 (15.7%) use cross-clamp and fibrillation techniques. Of those using cardioplegia, 76 (83.5%) use blood cardioplegia, 15 (19.7%) use warm-blood and 60 (78.9%) use cold-blood cardioplegia. 15(16.5%) use crystalloid cardioplegia. Retrograde cardioplegia is used by 23 (25.2%). We find an interesting variation of practice in relation to specifics like warm induction, graft cardioplegia, hot-shot, single cross-clamp, hypothermia and venting procedures. An overwhelming majority of surgeons performing OPCAB use the Octopus stabiliser (n=44, 77.2%) with some others preferring the Genzyme system. Supplementary stabilisation is not commonly used. While most OPCAB surgeons use intracoronary shunts (n=51), some prefer blockers (n=9) and others use coronary sloops (n=36). Ischaemic preconditioning is not commonly practised. Several surgeons have changed their practice of myocardial protection in the last 5 years (n=45). CONCLUSIONS: This survey gives us an interesting insight into current myocardial protection practices in the UK and Ireland and may be useful for future reference.