In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 7 ( 2021-7-8), p. e0252132-
Abstract:
The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination and is associated with progression in some cancers. We assessed MSI2 as potential clinical biomarker in colorectal cancer (CRC) and tubulovillous adenoma (TA) of colon mucosa. Methods We assessed 125 patients, of whom 20 had polyps of the colon (TAs), and 105 had CRC. Among 105 patients with CRC, 45 had stages I-III; among metastatic CRC (mCRC) patients, 31 had synchronous and 29 metachronous liver metastases. We used immunohistochemistry to measure MSI2 expression in matching specimens of normal tissue versus TAs, primary CRC tumors, and metastases, correlating expression to clinical outcomes. We analyzed the biological effects of depleting MSI2 expression in human CRC cells. Results MSI2 expression was significantly elevated in polyps versus primary tissue, and further significantly elevated in primary tumors and metastases. MSI2 expression correlated with decreased progression free survival (PFS) and overall survival (OS), higher tumor grade, and right-side localization (p = 0.004) of tumors. In metastases, high MSI2 expression correlated with E-cadherin expression. Knockdown of MSI2 in CRC cells suppressed proliferation, survival and clonogenic capacity, and decreased expression of TGFβ1, E-cadherin, and ZO1. Conclusion Elevated expression of MSI2 is associated with pre-cancerous TAs in the colonic mucosa, suggesting it is an early event in transformation. MSI2 expression is further elevated during CRC progression, and associated with poor prognosis. Depletion of MSI2 reduces CRC cell growth. These data imply a causative role of MSI2 overexpression at multiple stages of CRC formation and progression.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252132
DOI:
10.1371/journal.pone.0252132.g001
DOI:
10.1371/journal.pone.0252132.g002
DOI:
10.1371/journal.pone.0252132.g003
DOI:
10.1371/journal.pone.0252132.g004
DOI:
10.1371/journal.pone.0252132.t001
DOI:
10.1371/journal.pone.0252132.t002
DOI:
10.1371/journal.pone.0252132.t003
DOI:
10.1371/journal.pone.0252132.t004
DOI:
10.1371/journal.pone.0252132.s001
DOI:
10.1371/journal.pone.0252132.s002
DOI:
10.1371/journal.pone.0252132.s003
DOI:
10.1371/journal.pone.0252132.s004
DOI:
10.1371/journal.pone.0252132.s005
DOI:
10.1371/journal.pone.0252132.s006
DOI:
10.1371/journal.pone.0252132.r001
DOI:
10.1371/journal.pone.0252132.r002
DOI:
10.1371/journal.pone.0252132.r003
DOI:
10.1371/journal.pone.0252132.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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