Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma
Marinović, Sonja ; Škrtić, Anita ; Catela Ivković, Tina LU
; Poljak, Mirko
and Kapitanović, Sanja
(2021)
In Human Cell
34(5).
p.1455-1465
- Abstract
Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2). Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors,... (More)
Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2). Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors, 62.0% were positive for KRAS protein expression and there was a higher percentage of KRAS-positive tumor cells and a higher intensity of immunohistochemical reaction in T2 than in T1 samples. This could not be attributed to differences in KRAS mRNA levels, suggesting regulation via miR-544a-3p expression which was significantly decreased in T2 samples. Furthermore, we demonstrated that tumor samples carrying the KRAS-LCS6 variant allele had significantly higher protein expression of the wild-type KRAS. Our results suggest the role of the KRAS-LCS6 polymorphism and miR-544a-3p expression in the regulation of wild-type KRAS protein expression in sporadic CRC.
(Less)
- author
- Marinović, Sonja
; Škrtić, Anita
; Catela Ivković, Tina
LU
; Poljak, Mirko
and Kapitanović, Sanja
- publishing date
- 2021-09
- type
- Contribution to journal
- publication status
- published
- keywords
- Colon adenocarcinoma, Immunohistochemistry, KRAS, Let-7a, miR-544a
- in
- Human Cell
- volume
- 34
- issue
- 5
- pages
- 1455 - 1465
- publisher
- Springer
- external identifiers
-
- pmid:34235620
- scopus:85109418004
- ISSN
- 0914-7470
- DOI
- 10.1007/s13577-021-00576-2
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2021, Japan Human Cell Society.
- id
- aa2bd17d-b04c-4d0f-9947-6ddd3c6f3341
- date added to LUP
- 2026-09-20 00:15:53
- date last changed
- 2026-09-22 03:02:36
@article{aa2bd17d-b04c-4d0f-9947-6ddd3c6f3341,
abstract = {{<p>Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth. In this study, we investigated the KRAS status in correlation with clinicopathological features in sporadic CRC and more importantly the role of let-7a-5p and miR-544a-3p in the regulation of wild-type KRAS protein expression in the tumor center (T1) and invasive tumor front (T2). Analysis showed that 39.1% of tumor samples had KRAS mutations. In wild-type KRAS tumors, 62.0% were positive for KRAS protein expression and there was a higher percentage of KRAS-positive tumor cells and a higher intensity of immunohistochemical reaction in T2 than in T1 samples. This could not be attributed to differences in KRAS mRNA levels, suggesting regulation via miR-544a-3p expression which was significantly decreased in T2 samples. Furthermore, we demonstrated that tumor samples carrying the KRAS-LCS6 variant allele had significantly higher protein expression of the wild-type KRAS. Our results suggest the role of the KRAS-LCS6 polymorphism and miR-544a-3p expression in the regulation of wild-type KRAS protein expression in sporadic CRC.</p>}},
author = {{Marinović, Sonja and Škrtić, Anita and Catela Ivković, Tina and Poljak, Mirko and Kapitanović, Sanja}},
issn = {{0914-7470}},
keywords = {{Colon adenocarcinoma; Immunohistochemistry; KRAS; Let-7a; miR-544a}},
language = {{eng}},
number = {{5}},
pages = {{1455--1465}},
publisher = {{Springer}},
series = {{Human Cell}},
title = {{Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma}},
url = {{http://dx.doi.org/10.1007/s13577-021-00576-2}},
doi = {{10.1007/s13577-021-00576-2}},
volume = {{34}},
year = {{2021}},
}