Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation

Liu, Shiyang; Harmston, Nathan; Glaser, Trudy Lee; Wong, Yunka; Zhong, Zheng; Madan, Babita; Virshup, David M.; Petretto, Enrico

doi:10.1186/s13073-020-00788-5

Table 1 Wnt-regulated lncRNAs that affect HPAF-II cell growth in vivo and in vitro

From: Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation

Group	Ensembl Gene ID	Gene symbol	Gene biotype	log2FC^a (in vivo)	FDR^b (in vivo)	log2FC (in vitro)	FDR (in vitro)	Wnt-dependence	Nearest PCG	Correlation (nearest PCG)^c	*p value* of correlation	lncRNA-PCG Distance (bp)^d	Upregulated No. cancers^e	Downregulated No. cancers^f
in vitro and in vivo	ENSG00000276131	RP11-481J2.3	antisense	− 4.42	0.001	− 1.76	0.001	Wnt-Activated	GINS3	0.67	3.65E−06	97,726	6	0
in vitro and in vivo	ENSG00000188825	LINC00910	lincRNA	− 1.99	0.027	− 1.22	0.045	Wnt-Repressed	ARL4D	0.39	1.40E−02	9759	1	4
in vitro and in vivo	ENSG00000235823	LINC00263	lincRNA	− 1.85	0.029	− 2.67	0.001	Wnt-Repressed	SCD	0.54	4.04E−04	26,490	6	1
in vitro and in vivo	ENSG00000247844	CCAT1	lincRNA	− 1.20	0.001	− 0.99	0.033	Wnt-Activated	MYC	0.80	3.42E−08	516,345	9	3
in vivo	ENSG00000230177	RP5-1112D6.4	antisense	− 0.69	0.096	− 0.75	0.991	Wnt-Repressed	KIAA1919	− 0.24	1.29E−01	18,583	10	0
in vivo	ENSG00000230266	XXYLT1-AS2	antisense	1.77	0.098	− 0.46	0.471	Wnt-Repressed	XXYLT1	− 0.13	4.24E−01	123,295	1	7
in vivo	ENSG00000233895	RP1-122P22.2	lincRNA	− 1.65	0.015	− 1.18	0.158	Wnt-Repressed	RIN2	0.63	2.36E−05	128,812	0	10
in vivo	ENSG00000259146	RP1-261D10.2	antisense	0.22	0.063	0.12	0.541	Wnt-Activated	SIPA1L1	0.45	3.79E−03	1364	2	5
in vivo	ENSG00000259985	RP11-549B18.1	antisense	0.60	0.063	0.22	0.329	Wnt-Activated	B4GALT6	0.81	2.04E−08	180	6	4
in vivo	ENSG00000261662	RP5-1042I8.7	sense_overlapping	0.30	0.018	− 0.45	1.000	Wnt-Repressed	NOTCH2	0.40	1.19E−02	159,012	1	9
in vivo	ENSG00000233912	AC026202.3	antisense	0.66	0.063	0.29	0.295	Wnt-Activated	ARL8B	− 0.23	1.52E−01	65,108	2	7
in vivo	ENSG00000262903	RP11-235E17.6	antisense	0.48	0.063	− 0.01	1.000	Wnt-Repressed	CTNS	− 0.12	4.61E−01	21,623	8	1
in vivo	XLOC_052899	XLOC_052899	novel_lncRNAs	0.66	0.063	0.43	0.813	Wnt-Repressed	TMEM161B	0.68	2.75E−06	393,258	NA	NA
in vivo	ENSG00000234477	AC004231.2	antisense	0.96	0.018	0.09	0.974	Wnt-Repressed	KRT23	0.74	2.93E−07	16,203	5	2
in vivo	ENSG00000225969	ABHD11-AS1	antisense	0.79	0.018	0.04	0.849	Wnt-Repressed	ABHD11	0.69	1.75E−06	3828	9	3
in vivo	ENSG00000196421	LINC00176	lincRNA	0.57	0.063	0.25	0.823	Wnt-Activated	ZNF512B	0.09	5.76E−01	14,413	10	0
in vivo	ENSG00000272379	RP1-257A7.5	lincRNA	0.75	0.063	0.49	0.295	Wnt-Repressed	TBC1D7	− 0.13	4.30E−01	38,092	1	1
in vivo	XLOC_001141	XLOC_001141	novel_lncRNAs	0.81	0.063	− 0.24	1.000	Wnt-Activated	DEPDC1	0.08	6.35E−01	30,939	NA	NA
in vivo	XLOC_022655	XLOC_022655	novel_lncRNAs	0.67	0.084	0.20	0.813	Wnt-Activated	DIS3L	0.77	1.09E−07	42,903	NA	NA
in vivo	ENSG00000232536	RP11-74C1.4	sense_intronic	0.63	0.018	0.18	0.541	Wnt-Repressed	TUFT1	0.40	1.08E−02	210	5	2
in vivo	ENSG00000262468	LINC01569	lincRNA	0.56	0.063	0.62	0.160	Wnt-Activated	TFAP4	0.74	3.28E−07	19,285	9	1
in vivo	ENSG00000184224	C11orf72	lincRNA	0.52	0.063	0.36	0.272	Wnt-Repressed	NDUFV1	0.11	5.10E−01	145	3	2
in vivo	ENSG00000277692	RP11-358N2.2	lincRNA	0.50	0.063	− 0.27	1.000	Wnt-Repressed	ASXL1	− 0.36	2.43E−02	3290	3	3
in vivo	ENSG00000250413	RP11-448G15.1	antisense	0.43	0.063	0.03	0.849	Wnt-Repressed	SLC2A9	0.25	1.14E−01	48,453	2	9
in vivo	ENSG00000224660	SH3BP5-AS1	antisense	0.57	0.018	0.45	0.177	Wnt-Repressed	SH3BP5	− 0.36	2.44E−02	87,183	0	6
in vitro	ENSG00000233930	KRTAP5-AS1	antisense	− 0.09	0.794	− 0.50	0.036	Wnt-Activated	DUSP8	0.55	2.69E−04	566	7	2
in vitro	XLOC_033478	XLOC_033478	novel_lncRNAs	− 0.28	0.794	− 0.85	0.009	Wnt-Activated	ID2	0.28	8.11E−02	797,501	NA	NA
in vitro	XLOC_005971	XLOC_005971	novel_lncRNAs	0.58	0.834	− 0.82	0.036	Wnt-Activated	NSL1	0.02	8.94E−01	68,636	NA	NA
in vitro	ENSG00000249042	CTD-2015H6.3	antisense	− 0.21	0.640	0.55	0.015	Wnt-Activated	ZFYVE16	0.46	3.21E−03	80,049	6	4
in vitro	ENSG00000246889	AP000487.5	antisense	− 0.73	0.682	0.66	0.001	Wnt-Activated	CTTN	− 0.24	1.36E−01	83	8	3
in vitro	XLOC_036743	XLOC_036743	novel_lncRNAs	− 0.49	0.729	0.48	0.066	Wnt-Repressed	LGALSL	0.30	5.87E−02	78,230	NA	NA
in vitro	ENSG00000264301	LINC01444	lincRNA	− 0.43	0.908	0.76	0.070	Wnt-Repressed	RNMT	− 0.07	6.58E−01	1,243,807	2	0
in vitro	ENSG00000215256	DHRS4-AS1	antisense	0.28	0.569	0.63	0.070	Wnt-Activated	DHRS4L2	0.29	6.64E−02	18,964	2	5
in vitro	ENSG00000224046	AC005076.5	antisense	0.36	0.132	0.85	0.001	Wnt-Activated	DMTF1	− 0.38	1.64E−02	58	2	5

^alog2FC: the enrichment/depletion of sgRNAs targeting a lncRNA, calculated based on log2 transformed fold change of read counts of the second best sgRNA targeting the lncRNA. Positive FC means sgRNA targeting increased cell growth in the screen; negative FC means sgRNA targeting decreased cell growth in the screen
^bFDR, false discovery rate, calculated based on the fold change of all sgRNAs targeting the lncRNA compared to the non-targeting controls; FDR < 10% is highlighted in bold (see Methods)
^cCorrelation (nearest PCG): Spearman correlation coefficient of Wnt-regulated lncRNA with its nearest PCG in response to Wnt inhibition in the orthotopic HPAF-II cancer model
^dlncRNA-PCG distance (bp): the distance in base pair between the TSS of Wnt-regulated lncRNA and its nearest PCG; distance less than 1 kb is highlighted in italic, as the PCG may be suppressed by sgRNA targeting the lncRNA
^eUpregulated No. cancers: number of TCGA cancer types the lncRNA is upregulated, as determined by differential expression (FDR < 5%) between tumors and their paired normal samples
^fDownregulated No. cancers: number of TCGA cancer types the lncRNA is downregulated, as determined by differential expression (FDR < 5%) between tumors and their paired normal samples

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