Screening of Specific and Common Pathways in Breast Cancer Cell Lines MCF-7 and MDA-MB-231 Treated with Chlorophyllides Composites
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Chlorophyll Extraction and Measurement
2.3. Preparation of Chlorophyllides Composites by Using Chlorophyllase
2.4. Total RNA Preparation for Sequencing
2.5. Preparation of cDNA Library and Sequencing
2.6. Microarray Gene Expression Profiling
2.7. Quantitative Reverse Transcription PCR (RT-qPCR)
2.8. Statistical Analysis
3. Results and Discussion
3.1. DEG Analysis in MCF-7 and MDA-MB-231 Cells
3.2. GO Annotation of Differential Expessed Genes
3.3. KEGG Pathway Analysis of DEGs
3.4. Analysis of Common KEGG Pathways
3.5. Validation of RNA Expression by RT-qPCR
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
Abbreviations
(ANXA4) | annexin A4 |
(BP) | biological process |
(CC) | cellular component |
(CCR1) | chemokine C-C motif receptor 1 |
(TOP2A) | DNA topoisomerase II alpha 170 kDa |
(ER) | estrogen receptor |
(ETNK1) | ethanolamine kinase 1 |
(FC) | fold change |
(HER2) | human epidermal growth receptor 2 |
(RAP2B) | member of RAS oncogene family |
(MAGI1) | membrane associated guanylate kinase WW and PDZ domain containing 1 |
(MF) | molecular function |
(NLRC5) | NLR family CARD domain containing 5 |
(SLC7A7) | solute carrier family 7 membrane 7 |
(STIM2) | stromal interaction molecule 2 |
(PR) | progesterone receptor |
(PKN1) | protein kinase N1 |
(TNBC) | triple negative breast cancer |
(RT-qPCR) | quantitative reverse transcription PCR |
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Name | Sequence | Target Gene | Product Size (bp) |
---|---|---|---|
GAPDH-F | ATCACTGCCACCCAGA AGAC | GAPDH | 460 |
GAPDH-R | ATGAGGTCCACCACCCTGTT | ||
CCR1-F | AGAAGCCGGGATGGAAACTC | CCR1 | 165 |
CCR1-R | TTCCAACCAGGCCAATGACA | ||
STIM2-F | AGTCTTTGGGACTCTGCACG | STIM2 | 129 |
STIM2-R | TGTTGCCAGCGAAAAAGTCG | ||
ETNK1-F | CCAAAGCATGTCTGCAACCC | ETNK1 | 114 |
ETNK1-R | AAGCAGAAGCCTTGACCCTC | ||
RAP2B-F | AGCTTCCAGGACATCAAGCC | RAP2B | 190 |
RAP2B-R | AGGCTTTGTTTTTGGCCGAC | ||
MAGIL-F | GCCTTGCACAACCCGATCT | MAGIL | 150 |
MAGIL-R | GGCTTGGGTGTCCCATAATAG | ||
NLRC5-F | ACCTTAAGCCTGTGTCCACG | NLRC5 | 115 |
NLRC5-R | CTGTGAACCTGCCACAGCA | ||
SLC7A7-F | CTCACTGCTTAACGGCGTGT | SLC7A7 | 170 |
SLC7A7-R | CCAGTTCCGCATAACAAAGG | ||
PKN1-F | GCCATCAAGGCTCTGAAGAA | PKN1 | 136 |
PKN1-R | GTCTGGAAACAGCCGAAGAG | ||
TOP2A-F | CTTTGGCTCGATTGTTATTTCC | TOP2A | 142 |
TOP2A-R | CCCAGTACCGATTCCTTCAG |
Pathway ID | Pathway Description | Number of DEGs | All Genes with Pathway Annotation | q-Value | ||
---|---|---|---|---|---|---|
Up | Down | Total DEGs | ||||
hsa05202 | Transcriptional misregulation in cancer | 47 | 42 | 89 (3.749%) | 186 (2.347%) | 1.296 × 10−5 |
hsa05203 | Viral carcinogenesis | 34 | 40 | 74 (3.117%) | 201 (2.536%) | 0.0428029 |
hsa05205 | Proteoglycans in cancer | 35 | 55 | 90 (3.791%) | 204 (2.574%) | 0.0002796 |
hsa05210 | Colorectal cancer | 22 | 26 | 48 (2.022%) | 86 (1.085%) | 2.367 × 10−5 |
hsa05211 | Renal cell carcinoma | 17 | 12 | 29 (1.222%) | 69 (0.871%) | 0.0433838 |
hsa05212 | Pancreatic cancer | 15 | 22 | 37 (1.559%) | 69 (0.871%) | 0.0021288 |
hsa05213 | Endometrial cancer | 13 | 14 | 27 (1.137%) | 69 (0.871%) | 0.0159683 |
hsa05214 | Glioma | 17 | 17 | 34 (1.432%) | 69 (0.871%) | 0.0118167 |
hsa05215 | Prostate cancer | 25 | 23 | 48 (2.022%) | 97 (1.224%) | 0.0005016 |
hsa05216 | Thyroid cancer | 10 | 11 | 21 (0.885%) | 37 (0.467%) | 0.0032991 |
hsa05217 | Basal cell carcinoma | 9 | 15 | 24 (1.011%) | 63 (0.795%) | 0.1293504 |
hsa05218 | Melanoma | 15 | 16 | 31 (1.306%) | 72 (0.909%) | 0.0298569 |
hsa05219 | Bladder cancer | 9 | 9 | 18 (0.758%) | 41 (0.517%) | 0.0669118 |
hsa05220 | Chronic myeloid leukemia | 14 | 22 | 36 (1.516%) | 76 (0.959%) | 0.0045089 |
hsa05221 | Acute myeloid leukemia | 15 | 16 | 31 (1.306%) | 67 (0.845%) | 0.0118167 |
hsa05222 | Small cell lung cancer | 13 | 33 | 46 (1.938%) | 92 (1.161%) | 0.0005016 |
hsa05223 | Non-small cell lung cancer | 13 | 20 | 33 (1.390%) | 66 (0.833%) | 0.0029084 |
hsa05224 | Breast cancer | 34 | 27 | 61 (2.570%) | 147 (1.855%) | 0.0066776 |
hsa05225 | Hepatocellular carcinoma | 32 | 40 | 72 (3.033%) | 168 (2.120%) | 0.0016521 |
hsa05226 | Gastric cancer | 30 | 28 | 58 (2.443%) | 149 (1.880%) | 0.0283904 |
hsa05230 | Central carbon metabolism in cancer | 13 | 17 | 30 (1.264%) | 69 (0.871%) | 0.0286728 |
hsa05231 | Choline metabolism in cancer | 20 | 16 | 36 (1.516%) | 98 (1.237%) | 0.1137391 |
hsa05235 | PD-L1 expression and PD-1 checkpoint pathway in cancer | 14 | 21 | 35 (1.474%) | 89 (1.123%) | 0.0624114 |
Pathway ID | Pathway Description | Number of DEGs | All Genes with Pathway Annotation | q-Value | ||
---|---|---|---|---|---|---|
Up | Down | Total DEGs | ||||
hsa01521 | EGFR tyrosine kinase inhibitor resistance | 22 | 20 | 42 (1.769%) | 79 (0.997%) | 0.0002796 |
hsa01522 | Endocrine resistance | 24 | 21 | 45 (1.896%) | 98 (1.237%) | 0.0032168 |
hsa01523 | Antifolate resistance | 5 | 10 | 15 (0.632%) | 31 (0.391%) | 0.0464471 |
hsa01524 | Platinum drug resistance | 15 | 23 | 38 (1.601%) | 73 (0.921%) | 0.0006735 |
Description | Gene Name | Log2 FC * | KEGG Pathway |
---|---|---|---|
Up regulation (MCF-7-chlorophyllides/MDA-MB-231-chlorophyllides) | |||
annexin A4 | ANXA4 | 1.3495564 | hsa04974 |
C-C motif chemokine receptor 1 | CCR1 | 2.573958 | ko04060, ko04061, ko04062, ko05163, ko05167 |
stromal interaction molecule 2 | STIM2 | 1.4764014 | hsa04020 |
ethanolamine kinase 1 | ETNK1 | 1.1246655 | hsa00564, hsa01100 |
RAP2B, member of RAS oncogene family | RAP2B | 1.2477774 | NA |
BRCA2 and CDKN1A interacting protein | BCCIP | 1.0360939 | NA |
ribonucleotide reductase M2 B | RRM2B | 1.1502474 | hsa00230, hsa00240, hsa00480, hsa00983, hsa01100, hsa04115 |
cysteine-serine-rich nuclear protein 2 | CSRNP2 | 1.155312 | NA |
serine kinase H1 | PSKH1 | 1.1608988 | NA |
zinc finger and SCAN domain containing 16 | ZSCAN16 | 1.175633 | NA |
histone cluster 2, H3a | HIST2H3A | 1.2060455 | hsa04613, hsa05034, hsa05131, hsa05202, hsa05322 |
wingless-type MMTV integration site family, member 3A | WNT3A | 1.2382799 | hsa04150, hsa04310, hsa04390, hsa04550, hsa04916, hsa04934, hsa05010, hsa05022, hsa05165, hsa05200, hsa05205, hsa05206, hsa05217, hsa05224, hsa05225, hsa05226 |
acetyl-CoA carboxylase beta | ACACB | 1.2477973 | hsa00061, hsa00620, hsa00640, hsa01100, hsa04152, hsa04910, hsa04920, hsa04922, hsa04931 |
zinc finger protein 90 | ZNF90 | 1.4318171 | hsa05168 |
hyaluronan-mediated motility receptor | HMMR | 1.4742341 | ko04512 |
tribbles pseudokinase 2 | TRIB2 | 1.5311222 | NA |
Down- regulation (MCF-7-chlorophyllides/MDA-MB-231-chlorophyllides) | |||
membrane associated guanylate kinase, WW and PDZ domain containing 1 | MAGI1 | −1.2064317 | hsa04015, hsa04151, hsa04530, hsa05165 |
NLR family, CARD domain containing 5 | NLRC5 | −2.5420052 | NA |
solute carrier family 7 (amino acid transporter light chain, y+L system), member 7 | SLC7A7 | −4.4729806 | hsa04974 |
protein kinase N1 | PKN1 | −1.3322328 | hsa04151, hsa04621, hsa05132, hsa05135 |
topoisomerase (DNA) II alpha 170kDa | TOP2A | −1.1590858 | hsa01524 |
UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 6 | B4GALT6 | −3.2967566 | ko00600, ko01100 |
zinc finger protein 334 | ZNF334 | −2.4680017 | hsa05168 |
acyl-CoA synthetase short-chain family member 1 | ACSS1 | −2.1925126 | hsa00010, hsa00620, hsa00630, hsa00640, hsa01100, hsa01200 |
isovaleryl-CoA dehydrogenase | IVD | −1.8816549 | ko00280, ko01100 |
ADP-ribosylation factor-like 2 | ARL2 | −1.8091316 | NA |
Rho guanine nucleotide exchange factor 10 | ARHGEF10 | −1.9429478 | ko04270, ko04611, ko04810, ko04928, ko05130, ko05135, ko05163, ko05200, ko05205, ko05417 |
cyclin-dependent kinase 13 | CDK13 | −1.3298924 | NA |
diacylglycerol O-acyltransferase 2 | DGAT2 | −1.3269336 | ko00561, ko01100, ko04975 |
solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3 | SLC13A3 | −1.3249987 | NA |
nuclear receptor subfamily 1, group D, member 1 | NR1D1 | −1.2920206 | ko04710 |
zinc finger protein 76 | ZNF76 | −1.2438793 | hsa05168 |
ankyrin repeat domain 34A | ANKRD34A | −1.2280619 | NA |
salt-inducible kinase 2 | SIK2 | −1.2129109 | ko04922 |
v-myc avian myelocytomatosis viral oncogene homolog | MYC | −1.2045108 | ko04010, ko04012, ko04110, ko04151, ko04218, ko04310, ko04350, ko04390, ko04391, ko04550, ko04630, ko04919, ko05132, ko05160, ko05161, ko05163, ko05166, ko05167, ko05169, ko05200, ko05202, ko05205, ko05206, ko05207, ko05210, ko05213, ko05216, ko05219, ko05220, ko05221, ko05222, ko05224, ko05225, ko05226, ko05230 |
zinc finger protein 780A | ZNF780A | −1.1839843 | hsa05168 |
oligonucleotide/oligosaccharide-binding fold containing 1 | OBFC1 | −1.1801386 | NA |
lanosterol synthase | LSS | −1.163355 | ko00100, ko01100, ko01110, ko01130 |
zinc finger, DHHC-type containing 17 | ZDHHC17 | −1.1437738 | NA |
carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase | CAD | −1.1388409 | hsa00240, hsa00250, hsa01100, hsa01240 |
centrosomal protein 152kDa | CEP152 | −1.1385807 | NA |
hypoxia inducible factor 1, alpha subunit | HIF1A | −1.0661852 | ko04066, ko04137, ko04140, ko04212, ko04361 Axon regeneration ko04659, ko04919, ko05167, ko05200, ko05205, ko05211, ko05230, ko05231, ko05235 |
aldehyde dehydrogenase 3 family, member B1 | ALDH3B1 | −1.063386 | hsa00010, hsa00340, hsa00350, hsa00360, hsa00410, hsa00980, hsa00982, hsa01100 |
polymerase (DNA directed), epsilon 2, accessory subunit | POLE2 | −1.0376518 | ko03030, ko03410, ko03420 |
arginine methyltransferase 3 | PRMT3 | −1.0357205 | NA |
polymerase (RNA) I polypeptide E, 53kDa | POLR1E | −1.0155994 | ko03020 |
cytochrome P450, family 1, subfamily A, polypeptide 1 | CYP1A1 | −1.0129887 | ko00140, ko00380, ko00830, ko00980, ko01100, ko04913, ko05204 |
WD repeat containing, antisense to TP53 | WRAP53 | −1.0114268 | NA |
heat shock transcription factor 2 | HSF2 | −1.0091325 | ko03000 |
inositol monophosphatase domain containing 1 | IMPAD1 | −1.0071035 | ko00562, ko00920, ko01100, ko01120, ko01130, ko04070 |
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Huang, K.-S.; Wang, Y.-T.; Byadgi, O.; Huang, T.-Y.; Tai, M.-H.; Shaw, J.-F.; Yang, C.-H. Screening of Specific and Common Pathways in Breast Cancer Cell Lines MCF-7 and MDA-MB-231 Treated with Chlorophyllides Composites. Molecules 2022, 27, 3950. https://doi.org/10.3390/molecules27123950
Huang K-S, Wang Y-T, Byadgi O, Huang T-Y, Tai M-H, Shaw J-F, Yang C-H. Screening of Specific and Common Pathways in Breast Cancer Cell Lines MCF-7 and MDA-MB-231 Treated with Chlorophyllides Composites. Molecules. 2022; 27(12):3950. https://doi.org/10.3390/molecules27123950
Chicago/Turabian StyleHuang, Keng-Shiang, Yi-Ting Wang, Omkar Byadgi, Ting-Yu Huang, Mi-Hsueh Tai, Jei-Fu Shaw, and Chih-Hui Yang. 2022. "Screening of Specific and Common Pathways in Breast Cancer Cell Lines MCF-7 and MDA-MB-231 Treated with Chlorophyllides Composites" Molecules 27, no. 12: 3950. https://doi.org/10.3390/molecules27123950