scholarly journals Reactivation of Multiple Fetal miRNAs in Lung Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2686
Author(s):  
David E. Cohn ◽  
Mateus C. Barros-Filho ◽  
Brenda C. Minatel ◽  
Michelle E. Pewarchuk ◽  
Erin A. Marshall ◽  
...  

MicroRNAs (miRNAs) play vital roles in the regulation of normal developmental pathways. However, cancer cells can co-opt these miRNAs, and the pathways that they regulate, to drive pro-tumourigenic phenotypes. Characterization of the miRNA transcriptomes of fetal organs is essential for identifying these oncofetal miRNAs, but it has been limited by fetal sample availability. As oncofetal miRNAs are absent from healthy adult lungs, they represent ideal targets for developing diagnostic and therapeutic strategies. We conducted small RNA sequencing of a rare collection of 25 human fetal lung (FL) samples and compared them to two independent cohorts (n = 140, n = 427), each comprised of adult non-neoplastic lung (ANL) and lung adenocarcinoma (LUAD) samples. We identified 13 oncofetal miRNAs that were expressed in FL and LUAD but not in ANL. These oncofetal miRNAs are potential biomarkers for LUAD detection (AUC = 0.963). Five of these miRNAs are derived from the imprinted C14MC miRNA cluster at the 14q32 locus, which has been associated with cancer development and abnormal fetal and placental development. Additionally, we observed the pulmonary expression of 44 previously unannotated miRNAs. The sequencing of these fetal lung samples also provides a baseline resource against which aberrant samples can be compared.

2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. B19-B19
Author(s):  
Cecilia Menna ◽  
Mohsen Ibrahim ◽  
Daniela Peruzzi ◽  
Luca Pacini ◽  
Michela Ciancamerla ◽  
...  

2009 ◽  
Vol 41 (6) ◽  
pp. 448-455 ◽  
Author(s):  
Jinlian Hua ◽  
Haisheng Yu ◽  
Wuzi Dong ◽  
Chunrong Yang ◽  
Zhimin Gao ◽  
...  

1992 ◽  
Vol 32 (3) ◽  
pp. 350-355 ◽  
Author(s):  
Cynthia K Ewing ◽  
Diane M Duffy ◽  
James M Roberts

2010 ◽  
Vol 34 (8) ◽  
pp. S70-S70
Author(s):  
MingJie WANG ◽  
ZiQiang LUO ◽  
Mei LU ◽  
LiHong SHANG ◽  
ShaoJie YUE

1997 ◽  
Vol 273 (1) ◽  
pp. L227-L233 ◽  
Author(s):  
V. C. Venkatesh ◽  
H. D. Katzberg

Pulmonary epithelial Na+ channels (ENaC), composed of three distinct subunits (alpha, beta, and gamma), play a critical role in the regulation of fluid reabsorption from airspaces of late-gestation fetal lung. We studied the expression of ENaC subunit genes in cultured human fetal lung. All three mRNAs were expressed at low levels in second trimester lung (13-32% of adult values at 24 wk gestation). There was a spontaneous increase of approximately threefold over preculture values of all three subunits within 24 h of explant culture in serum-free Waymouth's medium. Dexamethasone (Dex) induced all three mRNAs by two- to threefold. Maximal induction was noted by 8 h with 30-100 nM Dex and half-maximal stimulation with 3-10 nM Dex. Cycloheximide decreased basal expression of all three subunits by 8 h but did not alter the response to Dex. Actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), inhibitors of RNA polymerase II, decreased the basal and the Dex-induced expression of all three subunits with a more marked effect on human hENaC-gamma than on hENaC-alpha or hENaC-beta. Under conditions where transcription was blocked by actinomycin D or DRB, Dex did not alter the stability of the three mRNAs. Triiodothyronine (T3) at low (2 nM) or high (100 nM) concentrations had no effect on the expression of the three subunits in the presence or absence of low (10 nM) or high (100 nM) concentrations of Dex for 8 or 24 h. Similarly, 8-bromoadenosine 3',5'-cyclic monophosphate (2 microM) had no effect on basal or Dex-induced increase in the three subunits. We conclude that the three Na+ channel subunit genes are expressed in second trimester human fetal lung and are coordinately upregulated by glucocorticoid hormones but not by T3 or adenosine 3',5'-cyclic monophosphate. Glucocorticoid induction is receptor mediated, is primarily transcriptional, and does not require the induction of an intermediate protein for transcriptional enhancement. We speculate that induction of lung ENaC may contribute to the beneficial effects of antenatal glucocorticoids in premature babies.


2011 ◽  
Vol 695 ◽  
pp. 393-396 ◽  
Author(s):  
Chang Mao Hung

Since the growing interest in the manufacture and environmental applications of nanocomposites consisting of CuO and TiO2nanoparticles (NPs), related toxicological effect and interaction with cellular structures for these newly developed materials are still unknown. Recent literature reveals that nanosized CuO and TiO2particles have cytotoxicity risks and ability to cause oxidative stress on health. This work considers the CuO doped TiO2nanocomposite particles were synthesized via a coprecipitation method with aqueous solutions as precursors of copper nitrateand titanium dioxide. Moreover, the nanocomposite particles were characterized using TGA-DTA, UV-Vis and TEM measurements. The calcination temperature was selected at 873 K. The nanocomposite particles were characterized by TEM, as the primary particles, aggregates ranged from 30 to 100 nm and have a good dispersion character. Cell cytotoxicity assessment and the percentage cell survival was determined by using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazoli um (MTS) assay on human fetal lung tissue cell (MRC-5). The experimental results show that the CuO doped TiO2nanocomposite particles cause potential cytotoxicity effect in cultured human cells.


1969 ◽  
Vol 41 (1) ◽  
pp. 298-311 ◽  
Author(s):  
Tom Elsdale ◽  
Robert Foley

Randomly seeded Petri dish cultures of embryonic human lung fibroblasts generate, in the course of their growth, highly ordered cellular arrangements. Thick, bilaterally symmetrical ridges with an axial polarity and an orthogonal, multilayered internal organization are observed within stationary cultures. The generation of these structures has been investigated. Ridges result from the spontaneous aggregation of cells in postconfluent cultures brought about by directed cell movements. These movements are promoted by the localized production of extracellular matrix sheets containing collagen, which provide new substrates for cellular colonization. Cells that have colonized one matrix substrate may secrete another above themselves, which will in turn be colonized. By a continuation of this cycle, thick stacks consisting of alternate layers of cells and matrix are produced to yield the observed aggregations. The distribution and shape of ridges in a culture imply that matrix substrates are confined to specific locations. The suggested control hypothesis assumes that all the cells in fibroblast cultures are potential producers of a single species of matrix. The serviceability of this matrix as a substrate for cellular colonization, however, is destroyed if the producer cells are motile. Matrix substrates, therefore, are only made by nonmotile cells.


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