Id |
Subject |
Object |
Predicate |
Lexical cue |
T428 |
0-23 |
Sentence |
denotes |
ACE2 and Other Diseases |
T429 |
24-78 |
Sentence |
denotes |
ACE2 is a multiform protein (Feng et al., 2010, 2011). |
T430 |
79-269 |
Sentence |
denotes |
As discussed above (section Structure of ACE2) its C-terminal domain is similar to collectrin, a kidney protein involved in amino acids trafficking and insulin secretion (Kuba et al., 2013). |
T431 |
270-382 |
Sentence |
denotes |
Alterations in ACE2 have been demonstrated in Hartnup’s disease due to a disturbance in amino acids homeostasis. |
T432 |
383-500 |
Sentence |
denotes |
Indeed, ACE2 has been proposed to modulate amino acid transport in bowel and gut microbiome (Hashimoto et al., 2012). |
T433 |
501-598 |
Sentence |
denotes |
Moreover, ACE2 participates in the regulation of metabolism, particularly of glucose homeostasis. |
T434 |
599-706 |
Sentence |
denotes |
In the pancreas, activation of the ACE2-Ang1-7-MasR pathway improves insulin secretion (Yuan et al., 2013). |
T435 |
707-893 |
Sentence |
denotes |
Obesity and high-fat diets cause a reduction in ACE2 expression in the adipose tissue, which in turn results in increased blood pressure (Gupte et al., 2008, 2012; Carsana et al., 2020). |
T436 |
894-1039 |
Sentence |
denotes |
A role for ACE2 is emerging in Alzheimer disease, since it has been shown that ACE2 can hydrolyse Beta amyloid peptides (Zou et al., 2007, 2013). |
T437 |
1040-1123 |
Sentence |
denotes |
There is also increasing evidence that the RAAS system may be implicated in cancer. |
T438 |
1124-1324 |
Sentence |
denotes |
ACE2 was found to inhibit cancer cell growth, metastasis, and angiogenesis in breast (Yu et al., 2016; Zhang Q. et al., 2019), pancreatic (Zhou et al., 2011), and colon cancer (Bernardi et al., 2012). |
T439 |
1325-1534 |
Sentence |
denotes |
Another study pointed out that hepatocellular carcinoma patients with higher levels of ACE2 had longer survival times, suggesting a positive link between ACE2 expression and better prognosis (Ye et al., 2015). |
T440 |
1535-1701 |
Sentence |
denotes |
Studies on human xenografts in mice clearly indicated that ACE2 inhibited tumor growth by suppressing invasion and angiogenesis in Non-Small Cell Lung Cancer (NSCLC). |
T441 |
1702-1975 |
Sentence |
denotes |
Remarkably, the same group demonstrated that overexpression of ACE2 promotes the expression of E-cadherin at expenses of mesenchymal markers such as vimentin, and thereby inhibits the epithelial-mesenchymal transition in NSCLC models (Feng et al., 2010; Qian et al., 2013). |
T442 |
1976-2182 |
Sentence |
denotes |
The discovery that lung cancer patients that harbor COVID-19 display more severe symptoms (Liang et al., 2020) set out intensive research on the possible connection between malignancies and ACE2 expression. |
T443 |
2183-2300 |
Sentence |
denotes |
A thorough bioinformatics analysis of the TCGA dataset on several kinds of cancer (Chai et al., 2020) has shown that: |
T444 |
2301-2369 |
Sentence |
denotes |
(1) Mutation and amplification of ACE2 gene are frequent in cancer. |
T445 |
2370-2475 |
Sentence |
denotes |
Yet, hot-spot mutation sites were never observed, as ACE2 mutations were distributed across all 18 exons. |
T446 |
2476-2732 |
Sentence |
denotes |
(2) ACE2 transcription was upregulated in six tumors: colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and lung adenocarcinoma (LUAD). |
T447 |
2733-2820 |
Sentence |
denotes |
Interestingly, ACE2 transcription was unchanged in lung squamous cell carcinoma (LUSC). |
T448 |
2821-2965 |
Sentence |
denotes |
(3) ACE2 transcription was downregulated in three tumors: testicular germ cell (TGCT), thyroid carcinoma (THCA), and kidney chromophobe (KICH). |
T449 |
2966-3121 |
Sentence |
denotes |
(4) Changes of ACE2 transcription were epigenetic in nature, as both mutation and copy variation of ACE2 did not correlate with its up- or downregulation. |
T450 |
3122-3226 |
Sentence |
denotes |
(5) In most cases, changes of ACE2 transcription strongly correlated with methylation in ACE2 promoter. |
T451 |
3227-3357 |
Sentence |
denotes |
More specifically, decreased methylation levels correlated with upregulation, whereas increased methylation led to downregulation. |
T452 |
3358-3445 |
Sentence |
denotes |
(6) No prognostic role of ACE2 expression on patient’s survival could be demonstrated. |
T453 |
3446-3566 |
Sentence |
denotes |
These data confirm the remarkable role of methylation in determining the ACE2 expression, as described in paragraph 2.2. |
T454 |
3567-3912 |
Sentence |
denotes |
Interestingly, a second bioinformatics study on Oncomine and TCGA databases gave slightly different results in terms of tumor-associated ACE2 expression changes, but confirmed the role of promoter hypomethylation in KIRP and uterine corpus endometrial carcinoma (UCEC) where ACE2 transcription was significantly upregulated (Yang et al., 2020a). |