LRIG1 expression and colorectal cancer prognosis

Bakherad, Maryam; Salimi, Mahdieh; Angaji, Seyed Abdolhamid; Mahjoubi, Frouzandeh; Majidizadeh, Tayebeh

doi:10.1186/s12920-020-00846-2

Cited by 4 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of LRIG1 is correlated with a better prognosis in several cancers, including non-small cell lung cancer 34,35 , breast cancer 24,36 , and hepatocellular carcinoma 37 . Although its expression is significantly lower in CRC than in normal colorectal tissue 24,38 , LRIG1 expression is not a prognostic biomarker in CRC at the protein and mRNA levels 38,39 . This low LRIG1 expression might be due to the suppression of LRIG1 by BMP, which is known to suppress the expression of murine intestinal epithelial stemness genes, including Lrig1 and Lgr5, via SMAD-mediated repression 40 .…”

Section: Discussionmentioning

confidence: 95%

Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer

Sasaki

Kondo

Onuma

et al. 2022

Preprint

View full text Add to dashboard Cite

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, the effect of the BMP pathway in colorectal cancer (CRC) is controversial; it can either be tumor promoting or tumor suppressing, depending on the study. In this study, we found that CRC cells reside in a BMP-rich environment based on RNA-sequencing database analysis. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of organoids in some CRC cases. CRC organoids treated with LDN193189 exhibited a decrease in epidermal growth factor receptor, which was, at least in part, mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1). Among CRC organoid panels from 18 different patients, suppression of organoid growth by BMP inhibition correlated with the induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, simultaneous treatment with LDN192189 and trametinib, an FDA-approved MEK inhibitor, resulted in a combination effect in both in vivo and in vitro xenograft tumor treatment in CRC organoids, which are susceptible to growth suppression by LDN193189. Taken together, the simultaneous inhibition of BMP and MEK can be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders.

show abstract

Section: Discussionmentioning

confidence: 95%

Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer

Sasaki

Kondo

Onuma

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The expression of LRIG1 is correlated with a better prognosis in several cancers, including non‐small‐cell lung cancer, 34,35 breast cancer, 24,36 and hepatocellular carcinoma 37 . Although its expression is significantly lower in CRC than in normal colorectal tissue, 24,38 LRIG1 expression is not a prognostic biomarker in CRC at the protein and mRNA levels 38,39 . This low LRIG1 expression might be due to the suppression of LRIG1 by BMP, which is known to suppress the expression of murine intestinal epithelial stemness genes, including Lrig1 and Lgr5 , through SMAD‐mediated repression 40 .…”

Section: Discussionmentioning

confidence: 99%

“…The expression of LRIG1 is correlated with a better prognosis in several cancers, including non-small-cell lung cancer, 34,35 breast cancer, 24,36 and hepatocellular carcinoma. 37 Although its expression is significantly lower in CRC than in normal colorectal tissue, 24,38 LRIG1 expression is not a prognostic biomarker in CRC at the protein and mRNA levels. 38,39 WT patients 41 and targeting EGFR and BRAF in BRAF-mutant patients.…”

Section: Discussionmentioning

confidence: 99%

“…37 Although its expression is significantly lower in CRC than in normal colorectal tissue, 24,38 LRIG1 expression is not a prognostic biomarker in CRC at the protein and mRNA levels. 38,39 WT patients 41 and targeting EGFR and BRAF in BRAF-mutant patients. 42 Inhibition of BMP could be an option for indirectly suppressing EGFR in combination with MEK inhibitors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK‐dependent colorectal cancer

et al. 2023

View full text Add to dashboard Cite

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context‐dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP‐rich environment based on curation of two publicly available RNA‐sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine‐rich repeats and immunoglobulin‐like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth‐suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA‐approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient‐derived organoids could offer functional biomarkers for predicting potential responders to this regimen.

show abstract

“…Because only a few references reveal that the expression of miR‑214‑3p in different subtypes of bladder cancer is also different, the expression and function of miR‑214‑3p in bladder cancer, as well as the regulatory mechanism, still need further research. Leucine-rich repeats and immunoglobulin-like domains 1 ( LRIG1 ) is a known tumor suppressor gene [ 28 ], and it has been proposed as a prognostic indicator for various malignancies, including prostate cancer [ 29 ], head-and-neck cancer [ 30 ], cutaneous squamous cell carcinoma [ 31 ], breast carcinoma [ 32 ], and uterine cervical carcinoma [ 33 ]. Furthermore, aberrant expression of LRIG1 has been identified as a significant factor in bladder carcinoma tumorigenesis and progression [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma

Cheng,

Li,

Liu

et al. 2024

Biol Direct

View full text Add to dashboard Cite

CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.

show abstract

LRIG1 expression and colorectal cancer prognosis

Cited by 4 publications

References 26 publications

Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer

Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK‐dependent colorectal cancer

Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma

Contact Info

Product

Resources

About