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  • Research Article   
  • Cell Mol Biol , Vol 70(1)

LncRNA Microarray Analysis of Non-small Cell Lung Cancer A549 Cell Lines Treated with Phycocyanin

Shuai Hao*, Boxiong Wu, Haozhe Cheng, Xinran Li, Wenjing Zhang and Qiancheng Li
Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, 100048, China
*Corresponding Author: Shuai Hao, Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing, 100048, China, Email: haoshuai@btbu.edu.cn

Received: 11-Dec-2023 / Manuscript No. cmb-23-122475 / Editor assigned: 14-Dec-2023 / PreQC No. cmb-23-122475 / Reviewed: 28-Dec-2023 / QC No. cmb-23-122475 / Revised: 04-Jan-2024 / Manuscript No. cmb-23-122475 / Published Date: 29-Jan-2024

Abstract

Phycocyanin is a type of marine food additive with multiple biological properties, including anticancer activity, but its underlying antineoplastic mechanism in non-small cell lung cancer (NSCLC) remains unclear. To investigate the underlying regulatory mechanism of phycocyanin in NSCLC, an LncRNA microarray analysis was performed using a phycocyanin-treated A549 cell model. The classification and expression of LncRNA s were determined. The profiles of differentially expressed LncRNA s were generated and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The results showed that 193 LncRNA s were upregulated and 116 LncRNA s were downregulated in the phycocyanin-treated group compared with the control group, and qRT‒ PCR analysis confirmed the expression of selected LncRNA s. Bioinformatic analysis indicated that the differentially expressed LncRNA s and their target genes were enriched in the extracellular region, epithelium development, NODlike receptor pathway, Notch signaling, and apoptosis process. In addition, coexpression network analysis identified 2,238 LncRNA‒mRNA, LncRNA‒LncRNA, and mRNA‒mRNA pairs. In particular, 72 etc. differentially expressed LncRNA target genes were discovered in the interaction network, which provides insights into the potential mechanism of phycocyanin in A549 cells. Moreover, cell phenotype experiments showed that downregulating the expression of LncRNA ENST00000538717, a LncRNA that is downregulated after phycocyanin treatment, could significantly inhibit the migration and viability of A549 and H460 cells. Consequently, this study lays a theoretical and potential foundation for NSCLC treatment and advances our understanding of the regulatory mechanisms of phycocyanin.

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Keywords

A549 cells; Anticancer; LncRNA; Non-small cell lung cancer (NSCLC); Phycocyanin

s

Introduction

Lung cancer remained the leading cause of cancer-related death in 2020, with an estimated 1.8 million deaths [1]. Non-small cell lung cancer (NSCLC), a subtype of lung cancer, accounts for approximately 85% of lung cancer cases and is characterized by high mortality and a low cure rate [2,3]. Currently, most NSCLCs are not effectively diagnosed at the early stage. Although treatments such as radiation therapy, chemotherapy or surgery have improved the survival rates of patients to a certain extent [4], the therapeutic efficacy of treatments for NSCLC is still very poor due to the lack of known biomarkers of NSCLC [4,5]. Therefore, in-depth research to identify specific biomarkers of NSCLC is urgently needed for the development of new drugs that effectively treat NSCLC.

Long noncoding RNAs (LncRNA s) are a class of regulatory RNA molecules that are larger than 200 nucleotides and have no protein-coding ability [6]. Unlike microRNAs and small nucleolar/ nuclear RNAs, LncRNA s have complex higher order structures [7]. It has been shown that the ectopic expression of LncRNA s is relevant to the occurrence and metabolism of lung cancer. Luo et al. reported that LncRNA TRERNA1 could promote the malignant progression of NSCLC by targeting FOXL1 [8]. Zhao et al. found that LncRNA SNHG14 also contributed to the growth of NSCLC via the miR-206/G6PD pathway [9]. In addition, some other LncRNA s, such as FENDRR, could exert antineoplastic effects on NSCLC cells by regulating the miR-761/TIMP2 axis [10]. Therefore, in-depth exploration of the regulatory role of LncRNA s in NSCLC and their mechanism is of great importance for the future treatment of NSCLC.

Phycocyanin, a pigment-protein complex derived from cyanobacteria, is a well-known natural food additive [11]. It has been revealed that phycocyanin, which is a potential natural antineoplastic factor, exerts antitumor effects on NSCLC [12,13]. Previously, we performed a miRNA-seq analysis and discovered that miR-6883- 3p, miR-3150a-3p, miR-642a-5p, and miR-627-5p were involved in the growth inhibitory effect of phycocyanin on NSCLC cells [14,15]. However, few studies have investigated the LncRNA expression profiles in phycocyanin-treated NSCLC cell lines. As LncRNA s are the upstream regulators of miRNAs in cells [16], further exploration of the expression profiles of LncRNA s participating in the phycocyaninmediated antineoplastic process is vital to elucidating the mechanism of phycocyanin-mediated inhibitory effects on NSCLC.

In the present study, to further investigate the precise antineoplastic regulatory mechanism of phycocyanin in NSCLC, a LncRNA-seq was performed to establish the LncRNA profile of NSCLC A549 cells after phycocyanin exposure. The results of this work are expected to explore the anti-tumor mechanism of phycocyanin at the molecular level, which undoubtedly laid a theoretical basis for the potential treatment of NSCLC with phycocyanin and provided insights into the regulatory mechanism of phycocyanin.

Materials and Methods

Study information

This work included experimental techniques such as cell migration and cell viability assays, RNA extraction, RNA-seq assay, qRT‒PCR, and bioinformatics analysis. The present work was performed in the labs of Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University in 2023.

Cell culture and sample treatment

A549 and H460 cells were cultured in DMEM supplemented with 0.1 mg/mL streptomycin, 100 units/mL penicillin and 10% fetal bovine serum (FBS) in a humidified atmosphere with 5% CO2 at 37 °C (American Type Cell Collection, ATCC, Manassas, VA, USA). Phycocyanin (95% purity) was purchased from Enviroloix (Portland, ME, USA). A549 cells were treated with phycocyanin or PBS as a control, followed by cell lysis and RNA extraction. The control groups were named Con-1, 2 and 3, and the phycocyanin-treated groups were named PC-1, 2 and 3.

RNA extraction and quality evaluation

The High Pure RNA isolation kit was employed for total RNA extraction according to the manufacturer’s specification (Roche, Penzberg, Germany). A Qubit fluorometer (Life Technologies, Eugene, OR, USA) with the Qubit RNA Assay Kit and NanoDrop-1000 instrument were used to evaluate the quality of RNA (Thermo Fisher Scientific Inc., Waltham, USA). The Agilent Bioanalyzer microcapillary electrophoresis system was used to assess RNA quality (Agilent, Santa Clara, CA, USA).

RNA sequencing

Two milligrams of polyA-minus RNA were used for cDNA library establishment. After total RNAs were extracted, mRNA and noncoding RNAs were enriched by removing rRNA, followed by fragmenting into short fragments (200-500 nt) using EpicentreRibo- Zero™ rRNA RemovalKit (Epicentre, WI, USA). RNA-sequencing libraries were generated under the instructions provided by NEB Next Ultra™ Directional RNA Library Prep kit forIllumina (New England BioLabs, Inc.). The Illumina HiSeqTM 2000 Sequencing System by Berry Genomics Inc. (Beijing, China) was employed for sequencing. Differential expression analysis for LncRNA from the database has proceeded. The sequencing reads were mapped to the reference genome using the TopHat program. A coding potential calculator assay was employed for evaluation. The quality control of raw data was performed using SeqPrep (https: //github.com/jstjohn/SeqPrep) and Sickle (https: //github.com/najoshi/sickle). TopHat2 (http: //ccb.jhu.edu/software/ tophat/index.shtml) was used for sequence comparative analysis after quality control. The Cufflinks software (http: //cole-trapnell-lab.github. io/cufflinks/) was employed for transcript assembly.

Analysis of differentially expressed (DE) LncRNA s

The number of mapped tags that was given by the raw expression levels of that particular LncRNA. To correct for differences in tag count between samples, the tag counts were scaled to CPM (count per millions) based on the total number of aligned tags. The analysis of differentially expressed LncRNA between control and phycocyanintreated samples was performed by edgeR. The setting was |logFC| > 1 & FDR < 0.05.

Target genes of LncRNA s and enrichment analysis

KEGG pathway analysis was employed for signal transduction pathway analysis of key genes. The p-value and gene count thresholds of KEGG analysis was p-adjust < 0.05 and 7, respectively. Gene Ontology (GO) analysis was used to identify important biological functions or processes of target genes. The p-value and gene count thresholds of GO analysis was p-adjust < 0.05 and 35, respectively.

qRT‒PCR

qRT‒PCR was performed by the Q6 qPCR system. GAPDH was used as the endogenous control gene. SYBR Green Master Mix was used for signal detection. The 2-ΔΔCT method was used to calculate the expression of each gene. The primer sequences of LncRNA and GAPDH for qRT‒PCR were as follows: forward: 5'-CGTTGCCTACAGTCAAGTCAGT- 3'; reverse: 5'-GCCATGGTTCCCTTACTGATAC-3'. Forward: 5'-TGTTCGTCATGGGTGTGAAC-3'; Reverse: 5'-ATGGCATGGACTGTGGTCAT- 3'.

Cell viability assay

Cells were cultured in 96-well plates, followed by LncRNA inhibitor incubation for 24 h. The MTT method was employed to determine the viability of A549 cells at 24 and 48 h. Briefly, MTT was added to each well for 4 h, followed by HCl-SDS lysis buffer and the cells were incubated for 24 h. The absorbance at 570 nm was recorded using a micro plate reader.

Cell migration assay

Cells were incubated with LncRNA inhibitor and cultured in 6-well plates. A pipette tip was used to scratch the cells and create a "wound". Each wound was observed at three different positions and its width was recorded. The three width values were averaged. The widths of the wounds were observed at 0 and 24 h. The cell migration rate was calculated from the difference in scratch width at 24 h over the original width (0 h).

Statistical Analysis

The data were analyzed by Microsoft Excel and GraphPad Prism. A two-tailed Student’s t test (paired t-test) was used for data analysis, and p < 0.05 indicated a significant difference between the control and test groups.

Results and Discussion

Classification and subgroup analysis of LncRNA s

Phycocyanin has been reported to exert effective antineoplastic effects on NSCLC cells [12,13]. Further investigation of the underlying anticancer mechanism of phycocyanin can help clarify the pathogenesis of NSCLC, laying the theoretical basis for lung cancer treatment. LncRNA s are well-known important molecules that regulate gene expressi

Sample Known lncRNA num Novel lncRNA num Total
Con-1 25,075 1,458 26,533
Con-2 24,543 1,464 26,007
Con-3 25,111 1,486 26,597
PC-1 25,334 1,468 26,802
PC-2 25,836 1,481 27,317
PC-3 25,738 1,483 27,221

Table S1: Statistics of lncRNAs.


Type		 Known lncRNA num Novel lncRNA num Total
Antisense 17768 1224 18992
Sense intron overlap 615 25 640
Intergenic 36889 207 37096
Sense exon overlap 6813 362 7175
Bidirection 5147 2 5149

Table S2: Classification and subgroup of lncRNAs.

on at the transcriptional, epigenetic, and posttranscriptional levels [17]. Numerous LncRNA s have been identified by highthroughput technology and are related to growth and development in cancer cells.

Over 26,000 LncRNA s (including known and novel LncRNA s) was identified in the Con and PC groups (Table S1). The chromosomal distribution and transcript types of LncRNA s were determined. In Table S2, of the antisense LncRNA s, the known LncRNA s accounted for 93.5%. Of the sense intron overlap, the known LncRNA s accounted for 96.1%. Of the intergenic LncRNA s, the known LncRNA s accounted for 99.4%. Of the sense exon overlap, the known LncRNA s accounted for 95.0%. Of the bidirectional LncRNA s, the known LncRNA s accounted for 99.9%.

Table S1: Statistics of lncRNAs.

Analysis of LncRNA expression and differentially expressed (DE) LncRNA s

As shown in Figure 1A, the LncRNA expression patterns of the Con and PC samples were similar, indicating the suitable replication of each experiment. Finally, 5,084 and 6,080 LncRNA transcripts were obtained from the Con and PC groups, respectively, after eliminating the single-exon, low-expression, and unreliable fragments. Of these, 4886 LncRNA s were found in both Con and PC samples (Figure 1B). Table S3 presents the top 15 LncRNA s that are expressed in the Con and PC groups based on TPM (transcripts per million reads). Strikingly, some LncRNA s was highly expressed in both the Con and PC groups, including ENST00000602361, ENST00000554988, ENST00000618589, and ENST00000659240. Some LncRNA s exhibited sample-specific expression. For instance, NONHSAT135828.2 and ENST00000508832 were specifically highly expressed in phycocyanin-treated A549 cells, while NONHSAT190639.1 and NONHSAT176665.1 were specifically highly expressed in control cells.

cellular-and-molecular-biology-expression

Figure 1: The expression analysis of lncRNAs. (A) The violin figure of expression pattern of lncRNAs in Con and PC groups. (B) Venn figure of the lncRNA numbers in Con and PC groups. (C) Heatmap of DE lncRNAs in each sample. Blue indicates low expression levels, red indicates high expression levels. (D) Number of DE lncRNAs between Con and PC groups. (E) Scatter diagram of DE lncRNAs. Red indicates upregulated lncRNAs, and green represents downregulated lncRNAs.

Con PC
lncRNAs TPM lncRNAs TPM
ENST00000602361 58511.15 ENST00000602361 64810.17
ENST00000554988 16530.64 ENST00000554988 14324.52
ENST00000618589 8645.37 ENST00000618589 7671.39
NONHSAT243766.1 6137.81 NONHSAT243766.1 6700.25
ENST00000659240 4918.28 ENST00000659240 5387.17
NONHSAT052027.2 2032.83 NONHSAT135828.2 2919.21
NONHSAT146442.2 1884.87 ENST00000610851 2154.29
ENST00000618227 1408.33 ENST00000618227 2010.76
ENST00000616691 1106.53 ENST00000616691 1871.71
NONHSAT021728.2 1076.28 NONHSAT052027.2 1701.58
ENST00000610851 1071.01 ENST00000508832 1288.08
ENST00000541782 994.52 ENST00000534336 1157.87
NONHSAT190639.1 910.08 NONHSAT021728.2 977.59
ENST00000534336 625.55 ENST00000541782 838.71
NONHSAT176665.1 594.18 NONHSAT146442.2 707.9

Table S3: The top expressed 15 lncRNA transcripts in Con and PC groups.

The heat map of differentially expressed LncRNA s showed that the expression patterns of LncRNA s within Con or PC samples were consistent, while the expression profiles between Con and PC groups exerted extremely significant differences (Figure 1C), indicating the effects of phycocyanin on the expression of LncRNA s in A549 cells. In total, 309 LncRNA s exhibited significant expression differences between the Con and PC groups, including 193 significantly upregulated and 116 significantly downregulated LncRNA s after phycocyanin treatment in A549 cells (Figure 1D). The scatter diagram of DE LncRNA s is shown in Figure 1E. The detailed information of DE LncRNA s was shown in Table S4. This LncRNA s is likely to be key LncRNA s that may act as downstream targets of phycocyanin in NSCLC cells. Table S5 shows the top 10 downregulated and top 10 upregulated LncRNA transcripts.

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Citation: Hao S, Wu B, Cheng H, Li X, Zhang W, et al. (2024) LncRNA MicroarrayAnalysis of Non-small Cell Lung Cancer A549 Cell Lines Treated with Phycocyanin.Cell Mol Biol, 69: 302.

Copyright: © 2024 Hao S, et al. This is an open-access article distributed underthe terms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium, provided the original author andsource are credited.

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lncRNA id lncRNA gene id FC(PC/Con) Log2FC(PC/Con) Pvalue Padjust Significant Regulate Con1 Con2 Con3 PC1 PC2 PC3 Con PC
ENST00000375633 ENSG00000204387 2.216937934 1.148568381 0.00064 0.00839 yes up 4.85 2.08 4.42 9.61 10.64 8.38 3.78333 9.54333
ENST00000375642 ENSG00000204387 2.252230455 1.171354456 0.00246 0.02563 yes up 0.82 0.84 1.31 1.79 3.19 2.62 0.99 2.53333
ENST00000383808 ENSG00000206567 2.194757374 1.134061462 0.00024 0.00365 yes up 0.19 0.21 0.14 0.46 0.49 0.43 0.18 0.46
ENST00000399543 ENSG00000215068 20.55209258 4.361213389 7.3E-05 0.00128 yes up 0 0 0.04 0.3 0.46 0.28 0.01333 0.34667
ENST00000399868 ENSG00000215244 74.36631846 6.216577447 0.00018 0.00285 yes up 0 0 0 0.25 0.09 0.06 0 0.13333
ENST00000413221 ENSG00000224032 0.497442355 -1.007398742 0.00198 0.02144 yes down 0.94 1.32 1.76 0.87 0.84 0.6 1.34 0.77
ENST00000416463 ENSG00000242282 58.76533342 5.876893433 0.00181 0.01999 yes up 0 0 0 0.9 0.24 2.18 0 1.10667
ENST00000418927 ENSG00000235269 0.0321649 -4.958369 0.0007 0.00903 yes down 0.09 0.12 0.19 0 0 0.01 0.13333 0.00333
ENST00000422944 ENSG00000228022 74.47820287 6.218746356 0.00042 0.00589 yes up 0 0 0 0.08 0.3 0.71 0 0.36333
ENST00000423477 ENSG00000225439 127.2206537 6.991189095 1.3E-05 0.00027 yes up 0 0 0 0.75 0.34 0.12 0 0.40333
ENST00000424518 ENSG00000228630 56.7453908 5.826431308 0.00018 0.00285 yes up 0 0 0 0.1 0.12 0.17 0 0.13
ENST00000424684 ENSG00000263590 2.676037221 1.420098183 4.5E-05 0.00083 yes up 0.14 0.1 0.18 0.36 0.52 0.39 0.14 0.42333
ENST00000426023 ENSG00000237807 0.204739826 -2.288136334 0.00154 0.01755 yes down 0.14 0.22 0.19 0.05 0.04 0.05 0.18333 0.04667
ENST00000428862 ENSG00000224596 2.373646048 1.24710482 0.00087 0.01084 yes up 0.24 0.22 0.2 0.72 0.42 0.68 0.22 0.60667
ENST00000430034 ENSG00000240801 4.690574082 2.229764506 2.6E-16 3.4E-14 yes up 4.07 2.77 2.9 17.97 19.01 15.26 3.24667 17.4133
ENST00000430373 ENSG00000227811 135.5234258 7.082398439 1.2E-07 4.1E-06 yes up 0 0 0 0.37 0.37 0.27 0 0.33667
ENST00000432735 ENSG00000215424 3.300294589 1.722594807 0.00066 0.00858 yes up 0.24 0.22 0.72 1.49 1.73 1.26 0.39333 1.49333
ENST00000434233 ENSG00000218510 0.358038271 -1.481814289 0.00102 0.0124 yes down 1.83 1.17 1.99 0.78 0.41 0.84 1.66333 0.67667
ENST00000435356 ENSG00000203392 2.104257514 1.073311269 3.2E-06 7.9E-05 yes up 0.8 0.7 0.67 1.68 1.56 2.01 0.72333 1.75
ENST00000439559 ENSG00000224914 2.551430127 1.351306133 2.6E-09 1.3E-07 yes up 0.5 0.45 0.62 1.62 1.28 1.68 0.52333 1.52667
ENST00000441052 ENSG00000235314 97.64557286 6.60948273 2.1E-06 5.5E-05 yes up 0 0 0 0.25 0.2 0.17 0 0.20667
ENST00000443596 ENSG00000234608 0.006900498 -7.179083786 1.8E-06 4.7E-05 yes down 1.6 0.75 0.37 0 0 0 0.90667 0
ENST00000443993 ENSG00000227619 0.009553142 -6.709809046 0.00024 0.00364 yes down 0.02 0.31 0.31 0 0 0 0.21333 0
ENST00000444503 ENSG00000232490 0.020634848 -5.5987734 0.00229 0.02411 yes down 1.29 0.4 0.18 0 0 0 0.62333 0
ENST00000444998 ENSG00000215424 0.043504416 -4.522694346 6.4E-06 0.00015 yes down 0.58 0.43 0.49 0.08 0 0 0.5 0.02667
ENST00000455395 ENSG00000230590 34.18808119 5.095421549 2.2E-05 0.00045 yes up 0.06 0 0 0.32 0.73 1.13 0.02 0.72667
ENST00000456953 ENSG00000196756 0.014481228 -6.109672284 0.00011 0.00184 yes down 0.63 0.23 0.27 0 0 0 0.37667 0
ENST00000457670 ENSG00000228412 0.017289583 -5.853953131 0.00061 0.00804 yes down 0.11 0.3 0.07 0 0 0 0.16 0
ENST00000458178 ENSG00000224086 2.081220275 1.057429667 5.3E-05 0.00095 yes up 0.04 0.05 0.04 0.12 0.09 0.1 0.04333 0.10333
ENST00000466953 ENSG00000254154 2.455148772 1.295810448 0.00474 0.04321 yes up 0.05 0.05 0.05 0.18 0.12 0.12 0.05 0.14
ENST00000475197 ENSG00000231177 39.90459136 5.318482845 1.3E-37 1.1E-34 yes up 0.14 0.16 0.03 5.69 4.92 4.71 0.11 5.10667
ENST00000488584 ENSG00000240875 0.003520513 -8.149998575 5.1E-09 2.4E-07 yes down 0.52 0.16 0.65 0 0 0 0.44333 0
ENST00000498979 ENSG00000245248 0.398254693 -1.328236734 0.00558 0.04934 yes down 0.34 0.48 0.26 0.17 0.16 0.18 0.36 0.17
ENST00000500698 ENSG00000245522 2.781788251 1.476012607 0.00048 0.0066 yes up 0.19 0.16 0.12 0.46 0.56 0.49 0.15667 0.50333
ENST00000501122 ENSG00000245532 2.811058729 1.491113595 1E-105 2E-101 yes up 18.09 15.14 18.49 59.35 52.11 55 17.24 55.4867
ENST00000503469 ENSG00000250041 0.027805182 -5.168502408 0.00385 0.03684 yes down 0.58 0.32 0.98 0 0 0 0.62667 0
ENST00000523313 ENSG00000249395 0.018744053 -5.737423242 0.00097 0.01187 yes down 0.49 0.23 1.17 0 0 0 0.63 0
ENST00000526566 ENSG00000255438 157.724407 7.301262117 0.00157 0.01777 yes up 0 0 0 0.6 0 0.46 0 0.35333
ENST00000534918 ENSG00000225138 3.284735992 1.71577742 3.8E-08 1.5E-06 yes up 0.37 0.3 0.19 1.11 1 1.12 0.28667 1.07667
ENST00000538717 ENSG00000231177 0.000963561 -10.01933648 5.9E-17 8.4E-15 yes down 4.64 3.6 4.4 0 0 0 4.21333 0
ENST00000547387 ENSG00000258017 0.359580402 -1.475613701 4.7E-06 0.00011 yes down 3.25 3.45 3.6 1.33 1.93 0.95 3.43333 1.40333
ENST00000550290 ENSG00000257354 16.18316295 4.016421701 8.7E-17 1.2E-14 yes up 0.02 0.04 0.09 0.71 0.84 1.17 0.05 0.90667
ENST00000555578 ENSG00000258701 120.6971396 6.915247676 1.1E-06 3.1E-05 yes up 0 0 0 0.18 0.23 0.38 0 0.26333
ENST00000562992 ENSG00000260693 2.434028955 1.28334633 5.1E-05 0.00093 yes up 1.39 1.35 0.99 3.94 3.18 3.29 1.24333 3.47
ENST00000569326 ENSG00000255182 2.01035948 1.007453498 0.00044 0.00616 yes up 0.28 0.27 0.24 0.55 0.71 0.57 0.26333 0.61
ENST00000571963 ENSG00000263072 0.012286251 -6.346811482 6.7E-05 0.00117 yes down 0.27 0.41 0.11 0 0 0 0.26333 0
ENST00000572035 ENSG00000255135 134.2814143 7.069115827 1.7E-06 4.5E-05 yes up 0 0 0 1.5 0.51 1.61 0 1.20667
ENST00000576232 ENSG00000224870 59.42880362 5.893090433 0.00014 0.00224 yes up 0 0.02 0 0.88 0.82 0.47 0.00667 0.72333
ENST00000602890 ENSG00000269888 0.487903558 -1.035332091 0.00435 0.0405 yes down 22.65 37.62 20.15 14.19 18.24 12.9 26.8067 15.11
ENST00000606343 ENSG00000272068 2.088855178 1.062712473 7E-10 3.8E-08 yes up 1.09 0.85 1.21 2.54 2.32 2.69 1.05 2.51667
ENST00000606892 ENSG00000231889 34.48069722 5.107717042 0.00037 0.0052 yes up 0 0 0.05 0.78 0.5 0.52 0.01667 0.6
ENST00000609111 ENSG00000272734 2.419563751 1.274746952 0.00064 0.00843 yes up 0.41 0.25 0.21 0.58 1.01 0.79 0.29 0.79333
ENST00000609983 ENSG00000234608 0.290601301 -1.782886935 0.00223 0.02364 yes down 2.59 3.9 3.04 0.3 1.25 1.56 3.17667 1.03667
ENST00000612722 ENSG00000275620 2.736120192 1.452131606 2.3E-08 9.2E-07 yes up 0.17 0.25 0.28 0.63 0.84 0.71 0.23333 0.72667
ENST00000615493 ENSG00000242086 0.007129691 -7.131944741 3.6E-06 9E-05 yes down 0.38 1.22 2.01 0 0 0 1.20333 0
ENST00000628917 ENSG00000242086 0.010493388 -6.574375663 6.2E-06 0.00014 yes down 2 1.33 0.86 0.04 0 0 1.39667 0.01333
ENST00000632919 ENSG00000233871 2.338666909 1.225686397 0.0021 0.0225 yes up 0.17 0.2 0.19 0.48 0.51 0.52 0.18667 0.50333
ENST00000648209 ENSG00000255248 69.55296901 6.120040195 6.4E-05 0.00113 yes up 0 0 0 0.2 0.11 0.09 0 0.13333
ENST00000650025 ENSG00000236204 137.239545 7.100552438 0.00235 0.02466 yes up 0 0 0 0.56 0.56 0 0 0.37333
ENST00000651080 ENSG00000234741 0.016455684 -5.925270221 0.00026 0.00381 yes down 0.5 0.12 0.34 0 0 0 0.32 0
ENST00000651958 ENSG00000280441 2.853676227 1.512821658 0.00104 0.0126 yes up 0.36 0.76 0.64 1.7 2.31 1.69 0.58667 1.9
ENST00000652379 ENSG00000280441 2.168376705 1.116615413 0.00308 0.03073 yes up 0.89 0.76 0.64 1.7 2.31 1.69 0.76333 1.9
ENST00000652496 ENSG00000230590 2.712508216 1.439627507 0.00093 0.01155 yes up 0.19 0.15 0.26 0.72 0.51 0.62 0.2 0.61667
ENST00000652746 ENSG00000233237 0.204178555 -2.292096749 0.00203 0.02194 yes down 0.6 0.61 0.4 0.18 0.17 0.02 0.53667 0.12333
ENST00000653437 ENSG00000253190 0.014712341 -6.08682934 6.9E-05 0.00121 yes down 0.31 0.63 0.34 0 0 0 0.42667 0
ENST00000653856 ENSG00000257261 0.015395207 -6.021374887 6.1E-05 0.00109 yes down 0.5 0.27 0.54 0 0 0 0.43667 0
ENST00000654005 ENSG00000225470 566.8307621 9.146774246 3E-11 2E-09 yes up 0 0 0 1 0.22 0.43 0 0.55
ENST00000654166 ENSG00000183250 105.6221692 6.722768866 0.00499 0.04512 yes up 0 0 0 0.25 0.34 0 0 0.19667
ENST00000654981 ENSG00000249406 55.73493256 5.800509933 0.0002 0.00313 yes up 0 0 0 0.34 0.19 0.24 0 0.25667
ENST00000655003 ENSG00000229043 90.72621219 6.503447523 0.00118 0.01404 yes up 0 0 0 0.23 0.02 0.62 0 0.29
ENST00000655030 ENSG00000231105 50.36628587 5.654386442 0.00067 0.00875 yes up 0 0 0 0.23 0.07 0.12 0 0.14
ENST00000655308 ENSG00000286483 0.047739545 -4.388671359 0.00455 0.04193 yes down 0.53 0.25 0.29 0 0 0.06 0.35667 0.02
ENST00000655351 ENSG00000272695 65.0106122 6.022603335 0.00014 0.00218 yes up 0 0 0 0.25 0.12 0.3 0 0.22333
ENST00000655606 ENSG00000223745 3.904617781 1.965181331 1E-06 2.8E-05 yes up 0.34 0.64 0.24 1.62 1.73 2.18 0.40667 1.84333
ENST00000656647 ENSG00000261824 0.025922263 -5.269664523 0.00426 0.03986 yes down 0.31 0.1 0.07 0 0 0 0.16 0
ENST00000656756 ENSG00000259583 3.744799819 1.9048886 0.00067 0.00869 yes up 0.13 0.21 0.61 1.74 1.09 1.23 0.31667 1.35333
ENST00000657056 ENSG00000286656 2.775175715 1.472579121 0.00432 0.04024 yes up 0.21 0.22 0.13 0.56 0.65 0.56 0.18667 0.59
ENST00000657070 ENSG00000230590 0.010255411 -6.607470867 7.9E-05 0.00137 yes down 0.08 0.52 0.26 0 0 0 0.28667 0
ENST00000657179 ENSG00000225470 154.6829687 7.273170548 0.00177 0.01963 yes up 0 0 0 0.18 0 0.3 0 0.16
ENST00000657211 ENSG00000249859 50.0528901 5.645381469 0.00502 0.04536 yes up 0 0 0 0.04 0.44 0.19 0 0.22333
ENST00000657677 ENSG00000261824 2.306289108 1.205573375 0.0045 0.04156 yes up 0.43 0.24 0.3 1.12 0.41 1.04 0.32333 0.85667
ENST00000657910 ENSG00000225470 0.00355346 -8.136559685 6.5E-10 3.5E-08 yes down 1.04 0.99 0.48 0 0 0 0.83667 0
ENST00000658183 ENSG00000255248 82.32441279 6.363248411 1E-05 0.00023 yes up 0 0 0 0.46 0.42 0.29 0 0.39
ENST00000658188 ENSG00000228889 15.44441864 3.949013661 0.00047 0.00647 yes up 0.06 0 0 0.39 0.36 0.3 0.02 0.35
ENST00000658695 ENSG00000231074 0.012796004 -6.288162859 0.00141 0.01628 yes down 0 0.09 0.08 0 0 0 0.05667 0
ENST00000658813 ENSG00000223546 0.196243661 -2.349282039 0.00128 0.01501 yes down 0.61 1.07 0.55 0.25 0.02 0.24 0.74333 0.17
ENST00000658859 ENSG00000224078 154.7157098 7.273475885 3.4E-08 1.3E-06 yes up 0 0 0 0.21 0.2 0.15 0 0.18667
ENST00000658963 ENSG00000227388 5.104968491 2.351902056 0.00076 0.00972 yes up 0.06 0.07 0.13 0.3 0.6 0.56 0.08667 0.48667
ENST00000659892 ENSG00000249859 0.023957439 -5.383382498 0.00124 0.01463 yes down 0.2 0.31 0.45 0 0 0 0.32 0
ENST00000659899 ENSG00000241316 91.38853589 6.513941295 4.7E-05 0.00085 yes up 0 0 0 0.32 0.07 0.18 0 0.19
ENST00000659912 ENSG00000249859 64.67391991 6.01511215 0.00122 0.01447 yes up 0 0 0 0.19 0.04 0.39 0 0.20667
ENST00000660010 ENSG00000257114 14.74642391 3.88229323 0.00116 0.0138 yes up 0 0.1 0 0.74 0.53 0.45 0.03333 0.57333
ENST00000660030 ENSG00000263753 0.008190606 -6.931814024 2.6E-07 8.5E-06 yes down 0.14 0.12 0.17 0 0 0 0.14333 0
ENST00000660248 ENSG00000236144 2.746065006 1.457365778 0.0005 0.00677 yes up 0.22 0.14 0.24 0.44 0.71 0.73 0.2 0.62667
ENST00000660374 ENSG00000223960 0.012959352 -6.269862557 1.7E-05 0.00035 yes down 0.27 0.19 0.34 0 0 0 0.26667 0
ENST00000660542 ENSG00000224078 169.7151079 7.406971188 0.00113 0.01355 yes up 0 0 0 0 0.18 0.18 0 0.12
ENST00000660547 ENSG00000255717 0.381074532 -1.3918549 0.00032 0.00465 yes down 4.02 1.66 4.28 1.11 1.52 1.67 3.32 1.43333
ENST00000660608 ENSG00000232931 3.358055155 1.747625926 1.6E-07 5.6E-06 yes up 0.27 0.2 0.24 0.96 0.89 0.92 0.23667 0.92333
ENST00000662234 ENSG00000248932 5.299729337 2.405918682 4.8E-05 0.00088 yes up 0.06 0.04 0.05 0.25 0.26 0.45 0.05 0.32
ENST00000662245 ENSG00000203875 0.019208769 -5.702091087 1.2E-05 0.00025 yes down 1.1 1.69 0.46 0 0 0.07 1.08333 0.02333
ENST00000662517 ENSG00000287300 0.049542159 -4.335199434 0.00081 0.01027 yes down 0.13 0.14 0.17 0.02 0 0 0.14667 0.00667
ENST00000662585 ENSG00000266903 15.17084775 3.923229801 0.00032 0.00463 yes up 0 0.01 0.06 0.49 0.56 0.21 0.02333 0.42
ENST00000662995 ENSG00000233828 0.093942816 -3.412073354 0.00538 0.04788 yes down 0.18 0.16 0.23 0 0 0.06 0.19 0.02
ENST00000663248 ENSG00000189223 67.35267698 6.073663383 8.4E-05 0.00144 yes up 0 0 0 0.06 0.05 0.02 0 0.04333
ENST00000663347 ENSG00000287275 2.049996816 1.035621669 0.00202 0.0218 yes up 0.37 0.26 0.22 0.64 0.66 0.69 0.28333 0.66333
ENST00000663448 ENSG00000203875 0.067900738 -3.880428928 0.00107 0.01291 yes down 0.54 0.54 0.53 0 0 0.13 0.53667 0.04333
ENST00000664934 ENSG00000263753 0.007109624 -7.136010945 2.5E-05 0.00048 yes down 0.04 0.43