Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex

Abstract

Background:Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is a functional long non-coding RNA (lncRNA), which is highly expressed in several tumours, including colorectal cancer (CRC). Its biological function and mechanism in the prognosis of human CRC is still largely under investigation.Methods:This study aimed to investigate the new effect mechanism of MALAT1 on the proliferation and migration of CRC cells in vitro and in vivo, and detect the expression of MALAT1, SFPQ (also known as PSF (PTB-associated splicing factor)), and PTBP2 (also known as PTB (polypyrimidine-tract-binding protein)) in CRC tumour tissues, followed by correlated analysis with clinicopathological parameters.Results:We found that overexpression of MALAT1 could promote cell proliferation and migration in vitro, and promote tumour growth and metastasis in nude mice. The underlying mechanism was associated with tumour suppressor gene SFPQ and proto-oncogene PTBP2. In CRC, MALAT1 could bind to SFPQ, thus releasing PTBP2 from the SFPQ/PTBP2 complex. In turn, the increased SFPQ-detached PTBP2 promoted cell proliferation and migration. SFPQ critically mediated the regulatory effects of MALAT1. Moreover, in CRC tissues, MALAT1 and PTBP2 were overexpressed, both of which were associated closely with the invasion and metastasis of CRC. However, the SFPQ showed unchanged expression either in CRC tissues or adjacent normal tissues.Conclusions:Our findings implied that MALAT1 might be a potential predictor for tumour metastasis and prognosis. Furthermore, the interaction between MALAT1 and SFPQ could be a novel therapeutic target for CRC.

Colorectal cancer carcinogenesis: a review of mechanisms

“…Mutations have also been identified in this fragment 185 . The higher expression of MALAT-1 is correlated with cell proliferation, migration, and invasion and observed in metastatic tumors 186 . MALAT-1 promotes tumor metastasis in nude mice by inhibiting the polypyrimidine tract binding protein 2 (PTBP2)/splicing factor proline/glutamine-rich (SFPQ) complex and releasing the oncogene PTBP2.…”

A potential biomarker for colorectal cancer: long non-coding RNA RP1-13P20.6

“…Recently, aberrantly expressed lncRNAs have been found related with CRC. As examples, lncRNAs such as CCAT1 [24][25], CCAT2 [26], HOTAIR [27] and MALAT1 [28] are increased in CRC tissues compared to NATs and have been identified as oncogenes. The lncRNAs can regulate the expression of their target genes, activate some signaling pathways, and promote cell proliferation, metastasis, and tumor recurrence [29][30][31][32].…”

Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications

“…A recent study indicated that the expression of MALAT-1 was higher in human CRC tissues than adjacent normal tissues (54). MALAT-1 upregulation has been demonstrated in CRC tumors.…”

“…Additionally, MALAT-1 may competitively bind to SFPQ to release SFPQ from the SFPQ/polypyrimidine tract binding protein 2 (PTBP2) complex in CRC LoVo cells. SFPQs, not PTBP2 proteins, are critical in the regulatory effect (54). In esophageal squamous cell carcinoma, MALAT-1 is suppressed by sex determining region Y (SRY)-box 17 via SRY binding-mediated transcriptional regulation (55).…”