Comprehensive Characterization of Integrin Subunit Genes in Human Cancers
9
Citation
27
Reference
10
Related Paper
Citation Trend
Abstract:
Although integrin subunit genes (ITGs) have been reported to be associated with some human cancer types, a systematic assessment of ITGs across human cancers is lacking. Hence, we performed comprehensive analyses to investigate mRNA expression, copy number variation (CNV), DNA methylation, mutation, and clinical landscapes of ITGs in more than 8000 cancer patients from The Cancer Genome Atlas (TCGA) dataset. Landscapes of ITGs were established across 20 human cancer types. We observed that ITGs are extensively dysregulated with heterogeneity in different system cancer types, part of which are driven by CNV, DNA hypomethylation or mutation. Furthermore, dysregulated prognosis-related ITGs were systematically identified in each cancer type, including ITGA11 in stomach adenocarcinoma (STAD). The models based on dysregulated ITGs with clinical relevance and TNM staging indexes are good indicators in STAD and head and neck squamous cell carcinoma. Finally, ITGA11 is overexpressed and associated with poor survival in STAD cases from the TCGA and additionally Gene Expression Omnibus cohorts. Functionally, ITGA11 knockdown inhibits malignant phenotypes in STAD cell lines AGS and MKN45, demonstrating the oncogenic role of ITGA11 in STAD. Together, this study highlights the important roles of ITGs in tumorigenesis as potential prognostic biomarkers, and provide an effective resource that identifies cancer-related genes of ITGs in human cancers.Cite
Citations (22)
<p>Chemoresistance properties of MUC16 and effect of cisplatin on apoptosis of MUC16 knockdown cells. A & B, MUC16 knockdown (H1975-shMUC16 seq1 and 2) cells were highly sensitive to cisplatin (A) and gemcitabine (B). C, The percentage of apoptotic cells was significantly higher in MUC16 knockdown cells (H292-shMUC16) treated with 5μM cisplatin. In contrast, no significant change was observed in the untreated scramble (H292-SCR) and MUC16 knockdown cells. D, We performed stable knockdown of Muc16 in K1418, the result shows that Muc16 is significantly decreased as compared to scramble cells. E, The p53 target gene p21 was significantly increased in MUC16 knockdown (H292-shMUC16) cells. *P<0.05, **P<0.01, ***P<0.001, and NS non-significant.</p>
Cite
Citations (0)
RNA-mediated interference (RNAi) has become a promising biopesticide technology with which to direct sequence-specific gene knockdown of key targets in the potato psyllid (PoP) Bactericera cockerelli, resulting in significant mortality. In this study, three strategically selected target genes, ATF4, C7 and D24, essential for the biosynthesis and regulation of ecdysteroids, were evaluated for knockdown and mortality using oral delivery of individual, paired and all three double-stranded RNAs (dsRNAs), in five replicated experiments. Knockdown was determined as the fold-change in gene expression using a quantitative polymerase chain reaction.Knockdown of the D24 target, at 39%-45%, resulted in 51% PoP mortality by 10 days post-ingestion (dpi) of dsRNA. Knockdown of C7, at 38%-61%, resulted in 53% mortality by 10 dpi, whereas dsD24 ingestion resulted in 65% mortality by 10 dpi when dsD24 and dsC7 were co-delivered. Three phenotypes, INCOMEC, PREMEC and SWOLLEN, were observed at a frequency of 4%-12%, and are consistent with incomplete ecdysis in immature and/or adult PoP. Adult PoP exhibiting INCOMEC survived for several days but were unable to mate or fly, whereas SWOLLEN and PREMEC were lethal to the immature instars. Knockdown of ATF4 did not result in the mortality or malformations in immature and adult PoP.Compared with knockdown of individual D24 and C7 targets, significantly greater RNAi penetrance was achieved following delivery of combined dsRNAs. The highest knockdown that resulted in incomplete ecdysis and/or mortality was obtained for targets with predicted involvement in the same or interacting pathway(s). Knockdown of ATF4 was apparently "rescued" by uncharacterized compensatory gene(s) or effects. © 2022 Society of Chemical Industry.
Knockdown resistance
RNA Silencing
Cite
Citations (8)
<p>Chemoresistance properties of MUC16 and effect of cisplatin on apoptosis of MUC16 knockdown cells. A & B, MUC16 knockdown (H1975-shMUC16 seq1 and 2) cells were highly sensitive to cisplatin (A) and gemcitabine (B). C, The percentage of apoptotic cells was significantly higher in MUC16 knockdown cells (H292-shMUC16) treated with 5μM cisplatin. In contrast, no significant change was observed in the untreated scramble (H292-SCR) and MUC16 knockdown cells. D, We performed stable knockdown of Muc16 in K1418, the result shows that Muc16 is significantly decreased as compared to scramble cells. E, The p53 target gene p21 was significantly increased in MUC16 knockdown (H292-shMUC16) cells. *P<0.05, **P<0.01, ***P<0.001, and NS non-significant.</p>
Cite
Citations (0)
Abstract We used the maternal-Gal4 shRNA system to knock down expression of dKDM5/lid in Drosophila melanogaster embryos, and analyzed the efficacy of the knockdown by qRT-PCR. Although average relative expression of lid was significantly lower in knockdown conditions compared to the driver-only control, we observed a wide and overlapping range of relative gene expression between individual control and knockdown embryos.
Cite
Citations (0)
We established TDP-43-silenced primary cortical neurons using lentivirus. We compared TDP-43 and FUS transcriptome profiles in primary cortical neurons. The sets of genes with altered expression levels upon TDP-43 knockdown or FUS knockdown overlapped by >25%. The sets of genes with altered exon splicing upon TDP-43 knockdown or FUS knockdown overlapped by >9%.
Cite
Citations (0)
<p>Stable knockdown of TSPYL5 in lung cancer cells. A, MUC16 expression was significantly elevated in cisplatin resistant cell line. To determine the TSPYL5 role in lung cancer, we stably knocked down TSPYL5 in H292 cells. B, Upon TSPYL5 knockdown, the expression of p53 was increased as compared to scramble cells. C, Knockdown of TSPYL5 was also confirmed by QPCR analysis. β-actin was used as loading control. **P<0.01.</p>
Cite
Citations (0)
Cite
Citations (0)
<p>Stable knockdown of TSPYL5 in lung cancer cells. A, MUC16 expression was significantly elevated in cisplatin resistant cell line. To determine the TSPYL5 role in lung cancer, we stably knocked down TSPYL5 in H292 cells. B, Upon TSPYL5 knockdown, the expression of p53 was increased as compared to scramble cells. C, Knockdown of TSPYL5 was also confirmed by QPCR analysis. β-actin was used as loading control. **P<0.01.</p>
Cite
Citations (0)
We recently developed a piggyback knockdown method that was used to knockdown genes in adult zebrafish. In this method, a vivo morpholino (VMO) piggybacks an antisense deoxyoligonucleotide (dO) into the somatic cells and reduces the cognate mRNA levels. In this paper, we tested whether we can piggyback more than one dO with one VMO. We designed various hybrids that had more than one dO that could be piggybacked with one VMO. We chose f7, f8, and αIIb genes and tested their knockdown by the appropriate assays. The knockdown with piggybacking either two or three dOs by one VMO yielded > 85% knockdown efficiency. We also performed knockdown of argonautes and rnaseh separately along with f7. We found the knockdown of f7 occurs when knockdown of argonautes happens and not when rnaseh knockdown was performed, suggesting that RNaseH is involved in mRNA degradation. In conclusion, we developed a method where we could knockdown three genes at one time, and by increasing the concentration of VMO by twofold, we could knockdown six genes simultaneously. These multiple gene knockdowns will not only increase the efficiency of the method in whole genome-wide knockdowns but will also be useful to study multifactorial disorders.
Cite
Citations (10)