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Page 4 of 7 Meng et al. J Cancer Metastasis Treat 2019;5:21 I http://dx.doi.org/10.20517/2394-4722.2018.96

Table 1. List of mRNAs encoding for mRNA splicing factors identified by MTDH PAR-CLIP or HITS-CLIP
Ref Seq# Gene #PAR-CLIP Ref Seq# Gene #PAR-CLIP
NM_006924 SRSF1 16 NM_004698 PRPF3 6
NM_003016 SRSF2 14 NM_014502 PRPF19 11
NM_003017 SRSF3* 7 NM_015629 PRPF31 3
NM_005626 SRSF4 8 NM_006109 PRMT5 7
NM_001039465 SRSF5 9 NM_014706 SART3 8
NM_006275 SRSF6 13 NM_018047 RBM22 5
NM_001031684 SRSF7 5 NM_012321 LSM4 5
NM_003769 SRSF9 7 NM_000344 SMN1 1
NM_054016 SRSF10 5 NM_015721 GEMIN4 11
NM_001190987 SRSF11 10 NM_015465 GEMIN5 4
NM_003090 SNRPA1 5 NM_024707 GEMIN7 3
NM_198216 SNRPB* 4 NM_024707 HNRNPA1* 7
NM_003093 SNRPC 5 NM_031157 HNRNPA2B1* 12
NM_006938 SNRPD1 3 NM_031243 HNRNPA3* 29
NM_004597 SNRPD2* 5 NM_194247 HNRNPH3* 10
NM_004175 SNRPD3 11 NM_012207 HNRNPK* 10
NM_003094 SNRPE 3 NM_002140 HNRNPL* 6
NM_003095 SNRPF 2 NM_001005335 HNRPU* 17
NM_003096 SNRPG 3 NM_004501 HNRNPUL2* 14
NM_022805 SNRPN 4 NM_001079559 PCBP1* 10

*MTDH interacting mRNAs identified in both High-throughput sequencing of RNA isolated by Cross-linking immunoprecipitation (HITS-
CLIP) and Photoactivatable Ribonucleoside-Enhanced Cross-linking and Immunoprecipitation (PAR-CLIP)

TDP43, CPEB2A/B AND ESRP1/RBFOX2 IN BREAST CANCER METASTASIS
[22]
Ke et al. reported that the loss of TDP43 (TAR DNA-binding protein 43), an important splicing regulator
involved in the SRSF3 regulated unique splicing of downstream gene PAR3, promotes metastasis in TNBC.
Highly expressed TDP43 is correlated with poor prognosis in TNBC. Knockdown of TDP43 inhibits
SRSF3 and PAR3 mediated metastasis. Two CPEB2 splicing isoforms with or without exon 4 was reported
to mediate opposing effects on cancer-related phenotypes. The CPEB2A isoform, which is produced by
exclusion of exon 4 from the mature CPEB2 mRNA, inhibited tumor growth. The CPEB2B splicing isoform
with the inclusion of exon 4 into the mature CPEB2 mRNA was overexpressed in aggressive forms of human
[23]
breast cancer and enhanced cancer metastasis was observed . CPEB2A/B promotes the translation of two
[23]
critical downstream proteins TWIST1 and HIF1a in the hypoxia/EMT pathway . Splicing factor ratio
might be an index of EMT and tumor aggressiveness in breast cancer. In fact, the association of low ESRP1/
RBFOX2 ratio with high risk of metastasis in early breast cancer was speculated to be a new early prognostic
[24]
marker of breast cancer metastasis .

RNA BINDING PROTEIN RBM47 INHIBITS BREAST CANCER METASTASIS BY REGULATING

SPLICING
RNA binding motif protein 47 (RBM47) was identified as a suppressor of breast cancer metastasis
through analysis of clinical breast cancer gene expression datasets, cell line models, and mutation data.
Transcriptome-wide HITS-CLIP analysis revealed widespread mRNAs associated with RBM47 by binding to
their introns and 3’UTRs. The dickkopf WNT signaling pathway inhibitor 1 (DKK1) is one of downstream
mRNAs of RBM47. RBM47 inhibits breast cancer metastasis by increasing stability of the Wnt antagonist
[25]
DKK1 .

NON-CODING RNA REST-003 PROMOTES BREAST CANCER METASTASIS