Identification of a novel interplaying loop of PPARγ and respective lncRNAs are involved in colorectal cancer progress

Hajipour, Maral; Mokhtari, Khatereh; Mahdevar, Mohammad; Esmaeili, Maryam; Peymani, Maryam; Nasr‐Esfahani, Mohammad Hossein; Mirzaei, Sepideh; Hasehmi, Mehrdad; Hushmandi, Kiavash; Ghaedi, Kamran

doi:10.1016/j.ijbiomac.2022.07.247

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…To achieve this, many studies has been conducted to investigate the role of long non-coding RNAs (lncRNAs) in modulating various biological processes of CRC cells through intricate lncRNA–mRNA regulatory networks. These studies aim to shed light on the initiation, progression, and metastasis of CRC, ultimately leading to improved strategies for early detection, effective treatment, and better patient outcomes [ 4 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Samadi,

Shahnazari,

Shekari

et al. 2023

Cancer Cell Int

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The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA–mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1’s aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1’s engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1’s potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.

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Section: Introductionmentioning

confidence: 99%

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Samadi,

Shahnazari,

Shekari

et al. 2023

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…To achieve this, many studies has been conducted to investigate the role of long non-coding RNAs (lncRNAs) in modulating various biological processes of CRC cells through intricate lncRNA-mRNA regulatory networks. These studies aim to shed light on the initiation, progression, and metastasis of CRC, ultimately leading to improved strategies for early detection, effective treatment, and better patient outcomes [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Samadi,

Shahnazari,

Shekari

et al. 2023

Preprint

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The HAND2-AS1 (HAND2 Antisense RNA 1) lncRNA has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Long noncoding RNAs (lncRNAs) are rising as essential regulators of gene expression and pivotal contributors to immune modulation. Here, based on the co-expression network analysis and construction of interacting lncRNA-mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1's aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1's engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8 + T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1's potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The heightened HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic stratagem, and a focal point for immunotherapeutic interventions.

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“…The effect of oxidative stress mainly involves reactive nitrogen species (RNS) and reactive oxygen species (ROS) as an outcome of chemical reactions; the resulting effect is often seen as a double-edged sword, with great controversy over the tumor-promoting and tumor-suppressing effects [6,10], the specific effect of ROS levels on tumor cells themselves, [11] sensitivity and lack of oxygen, and the tumor microenvironment of regulatory factors. When the content of ROS is insufficient to break the balance between oxidative and antioxidant systems in the tumor growth environment, it can participate in the regulation of epithelialmesenchymal transition (EMT), tumor angiogenesis, and other processes by activating PI3K/Akt and NF-κB signaling pathways [12][13][14]. ROS can also promote the metastasis and proliferation of tumor cells [15].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity

Chen

Mei

Xiao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Oxidative stress is crucial to the biology of tumors. Oxidative stress’ potential predictive significance in colorectal cancer (CRC) has not been studied; nevertheless here, we developed a forecasting model based on oxidative stress to forecast the result of CRC survival and enhance clinical judgment. The training set was chosen from the transcriptomes of 177 CRC patients in GSE17536. For validation, 65 samples of colon cancer from GSE29621 were utilized. For the purpose of choosing prognostic genes, the expression of oxidative stress-related genes (OXEGs) was found. Prognostic risk models were built using multivariate Cox regression analysis, univariate Cox regression analysis, and LASSO regression analysis. The outcomes of the western blot and transcriptome sequencing tests were finally confirmed. ATF4, CARS2, CRP, GPX1, IL1B, MAPK8, MRPL44, MTFMT, NOS1, OSGIN2, SOD2, AARS2, and FOXO3 were among the 14 OXEGs used to build prognostic characteristics. Patients with CRC were categorized into low-risk and high-risk groups according on their median risk scores. Cox regression analysis using single and multiple variables revealed that OXEG-related signals were independent risk factors for CRC. Additionally, the validation outcomes from western blotting and transcriptome sequencing demonstrated that OXEGs were differently expressed. Using 14 OXEGs, our work creates a predictive signature that may be applied to the creation of new prognostic models and the identification of possible medication candidates for the treatment of CRC.

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Identification of a novel interplaying loop of PPARγ and respective lncRNAs are involved in colorectal cancer progress

Cited by 8 publications

References 25 publications

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity

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