Silencing of brain-expressed X-linked 2 (BEX2) promotes colorectal cancer metastasis through the Hedgehog signaling pathway

Abstract

The incidence of colorectal cancer is increasing, and cancer metastasis is one of the major causes of poor outcomes. BEX2 has been reported to be involved in tumor development in several types of cancer, but its role in metastatic colorectal cancer remains largely undefined. Herein, we demonstrated that BEX2 knockout resulted in enhanced migratory and metastatic potential in colorectal cancer cells both in vitro and in vivo, and re-expression of BEX2 in knockout cells could reverse the enhanced migratory capacity. RNA-Seq results indicated that the hedgehog signaling pathway was activated after BEX2 knockout; moreover, the hedgehog signaling inhibitors, GANT61 and GDC-0449 could reverse the migratory enhancement of BEX2-/-colorectal cancer cells. We also demonstrated that the nuclear translocation of Zic2 after BEX2 silencing could activate the hedgehog signaling pathway, while Zic2 knockdown abrogated the migratory enhancement of BEX2-/-cells and inhibited the hedgehog signaling pathway. In summary, our findings suggest that BEX2 negatively modulates the hedgehog signaling pathway by retaining Zic2 in the cytoplasm in colorectal cancer cells, thereby inhibiting migration and metastasis of colorectal cancer cells.

AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1

“…Numerous studies have demonstrated that aberrant Gli1 expression in Hedgehog pathway plays a critical role in the development of CRC [ 20 , 26 ] and Gli1 promotes EMT in CRC cells [ 27 , 28 ]. Thus, we speculated whether Gli1 is regulated by AIM2 in CRC cells.…”

“…The Hedgehog (Hh) signaling pathway plays an essential role in cancer development and progression [ 19 , 20 ]. Gli1, as a key transcriptional factor of Hh pathway, has been proposed as a candidate oncogene in CRC [ 20 , 26 , 27 ]. In the present study, we found that AIM2 regulated Gli1 expression in CRC cells, which is evidenced by the following observations.…”

Induced pluripotent stem cells established from a female patient with Xq22 deletion confirm that BEX2 escapes from X‐chromosome inactivation

“…The brain expressed X‐linked genes are included in a group of genes that reside on the X‐chromosome with clustering and related to transcriptional regulation and signaling pathways in neurodegeneration, cell cycle and tumor growth 19 . Especially, BEX2 is included in the regulation of the transcriptional activity of oligomeric DNA binding complex containing LMO2 and NSCL2 20 .…”

Proteoform Identification by Combining RNA-Seq and Top-Down Mass Spectrometry

“…An RNA-seq data set of DLD-1 colorectal cancer cells (SRR6929326) was download from the sequence read archive (SRA), which contain 48.8 million paired short reads (150 bp). The RNA sample was prepared using the Illumina TruSeq RNA Sample Preparation protocol and deeply sequenced with an Illumina HiSeq 3000 42 . Phred quality scores (Q score) reported by FastQC (version 0.11.8) 43 showed that more than 90% of the short reads reached Q30 (99.9% base call accuracy).…”