LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT

Ji, Liechen; Chen, Shuo; Gu, Lixu; Wang, Juan

doi:10.2147/cmar.s260371

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…It was implicated in regulating fibroblast growth factor receptor 1 (FGFR1) expression in CRC by sponging microRNA-497, and its up-regulation was associated with poor patient survival [ 10 ]. Other studies have suggested that PUNISHER and LINC-PINT may create a negative feedback regulation loop in colon cancer [ 51 ]. Furthermore, PUNISHER could induce endothelial–mesenchymal transition (EMT) and increase CRC cell proliferation, motility, and invasion via targeting the miR-4,668-3p/SRSF1 axis [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

et al. 2022

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Objective: Colon cancer (CC) remains one of the leading causes of cancer death worldwide. Several mutations/polymorphisms have been implicated in CC development and/or progression. The role of the recently identified variants related to the long non-coding RNAs (lncRNAs) family has not yet been fully uncovered. In this sense, we aimed to explore the association between the lncRNA PUNISHER rs12318065 variant and the CC risk and/or prognosis. Methods: A total of 408 CC (paired 204 cancer/non-cancer) tissues were genotyped using the TaqMan allelic discrimination assay. Results: “A” variant was associated with higher susceptibility to develop CC under heterozygote (A/C vs. C/C: OR=1.39, 95%CI=1.09-2.17, p=0.002), homozygote (A/A vs. C/C: OR=2.63, 95%CI=1.51-4.58, p=0.001), dominant (A/C-A/A vs. C/C: OR=1.72, 95%CI=1.15-2.57, p=0.008), and recessive (A/A vs C/C-A/C: OR=2.23, 95%CI=1.34-3.72, p=0.001) models. Patients with metastasis were more likely to harbor A/A and A/C genotypes (16.7% and 14.1%) than 11% with the C/C genotype (p=0.027). Patients harboring C>A somatic mutation were more likely to develop relapse (52.6% vs. 26.5%, p=0.003), have poor survival (57.9% vs. 27.7%, p=0.001), and have shorter disease-free survival (43.2 ± 2.6 months vs. 56.8 ± 1.29 months, p<0.001) and overall survival (49.6 ± 2.4 months vs. 56.6 ± 0.99 months, p<0.001). Multivariate Cox regression analysis showed that patients with distal metastasis and C>A somatic mutation were three times more likely to die. Conclusions: To our knowledge, this study is the first to identify that the PUNISHER rs12318065 variant could be a novel putative driver of colon cancer and is associated with poor prognosis.

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Section: Discussionmentioning

confidence: 99%

PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

et al. 2022

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“…LINC-PINT inhibits tumor cell invasion to suppress cancer progression. LncRNA AGAP2-AS1 overexpression and LINC-PINT form a negative feedback loop on colon cancer cell proliferation, migration, and invasion [122]. The expression of LncRNA NEAT1 is closely related to the overall survival of colon cancer patients, and overexpression of NEAT1 can significantly promote the migration and invasion of colon cancer cells by competitively and endogenously binding to miR-185-5p to regulate IGF2 [123].…”

Section: Lncrnas and Colon Cancermentioning

confidence: 99%

The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

Lu,

Liang,

Meng

et al. 2023

Biomolecules

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The gut is the body’s largest immune organ, and the intestinal barrier prevents harmful substances such as bacteria and toxins from passing through the gastrointestinal mucosa. Intestinal barrier dysfunction is closely associated with various diseases. However, there are currently no FDA-approved therapies targeting the intestinal epithelial barriers. Long noncoding RNAs (lncRNAs), a class of RNA transcripts with a length of more than 200 nucleotides and no coding capacity, are essential for the development and regulation of a variety of biological processes and diseases. lncRNAs are involved in the intestinal barrier function and homeostasis maintenance. This article reviews the emerging role of lncRNAs in the intestinal barrier and highlights the potential applications of lncRNAs in the treatment of various intestinal diseases by reviewing the literature on cells, animal models, and clinical patients. The aim is to explore potential lncRNAs involved in the intestinal barrier and provide new ideas for the diagnosis and treatment of intestinal barrier damage-associated diseases in the clinical setting.

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“…LINC-PINT is also downregulated in colon cancer tissues but the main reported mechanistic interaction involving the oncogenic lncRNA AGAP2-AS1 appears presently unique to CRC. A negative correlation between AGAP2-AS1 and LINC-PINT was reported in CRC tissues with in vitro analysis showing that LINC-PINT affected the proliferation, invasion and migration of CRC cells by altering the expression of AGAP2-AS1 (Table 1; Ji et al, 2021). CNVs in protein coding genes along with gene copy number variations (CNVs) are widely studied as possible causes of the malignancy but these parameters in lncRNA genes are largely ignored.…”

Section: Colon Cancermentioning

confidence: 99%

PINTology: A short history of the lncRNA LINC‐PINT in different diseases

et al. 2022

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LINC-PINT is a p53-induced long intergenic noncoding transcript that plays a crucial role in many diseases, especially cancer. This long noncoding RNA (lncRNA) gene produces in total 102 (LNCipedia) alternatively spliced variants (LINC-PINT:1 to LINC-PINT:102). The functions of known variants include RNA transcripts, host transcripts for circular RNA (circRNA) generation and as sources for the translation of short peptides. In most human tumors, LINC-PINT is down-regulated where it serves as a tumor suppressor. However, the diversity of its functions in other maladies signifies its general clinical importance. Current LINC-PINT molecular functions include RNA-protein interactions, miRNA sponging and epigenetic modulation with these mechanisms operating in different cellular contexts to exert effects on biological processes ranging from DNA damage responses, cell cycle and growth arrest, senescence, cell migration and invasion, and apoptosis. Genetic polymorphisms in LINC-PINT have also been functionally associated with cancer and other pathologies including the autoimmune diseases pemphigus foliaceus and arthritis. Hence, LINC-PINT shows great potential as a clinical biomarker, especially for the diagnosis and prognosis of cancer. In this review, we explore the current knowledge highlighting the distinctive molecular functions of LINC-PINT in specific cancers and other disease states.Ihtisham Bukhari and Muhammad Riaz Khan contributed equally to this study.

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LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT

Cited by 8 publications

References 21 publications

PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

PINTology: A short history of the lncRNA LINC‐PINT in different diseases

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LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT

Cited by 8 publications

References 21 publications

PUNISHER rs12318065 C&gt;A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

PUNISHER rs12318065 C&gt;A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

PINTology: A short history of the lncRNA LINC‐PINT in different diseases

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PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer

PUNISHER rs12318065 C>A transversion: a putative somatic driver mutation for poor prognosis in colon cancer