Regulation of miR-186-YY1 axis by the p53 translational isoform ∆40p53: implications in cell proliferation

Katoch, Aanchal; Tripathi, Sonam; Pal, Apala

doi:10.1080/15384101.2021.1875670

Cited by 4 publications

(9 citation statements)

References 30 publications

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“…Recent observations also suggest a role for Δ40p53 as a tumor suppressor in hepatocellular carcinoma (16). Our latest studies showed that Δ40p53 can regulate miR-186-5p independent of full length p53 (17).…”

Section: Introductionmentioning

confidence: 73%

“…Thus far, the results obtained in this study indicate that Δ40p53 can regulate long noncoding RNAs in addition to miRNAs (17). Therefore, it is important to understand how LINC00176 functions in cells and what its mechanism of action could be (Figure 4A).…”

Section: Deciphering the Mechanism Of Action Of Linc00176mentioning

confidence: 79%

“…Recent observations also suggest a role for Δ40p53 as a tumor suppressor in hepatocellular carcinoma (Ota, Nakao et al 2017). Our latest studies showed that Δ40p53 could regulate miR-186-5p independent of full-length p53 (Katoch, Tripathi et al 2021). However, some studies have examined the functional role of Δ40p53; there has been little detailed investigation regarding intermediate molecules (such as RNAs or proteins) through which Δ40p53 exerts its influence on cells.…”

Section: Introductionmentioning

confidence: 99%

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The “LINC” in between Δ40p53-miRNA axis in the regulation of cellular homeostasis

Pal

2022

Preprint

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Recently, we showed that Δ40p53, the translational isoform of p53, can inhibit cell growth independently of p53 by regulating microRNAs. Here, we explored the role of Δ40p53 in regulating the lncRNA-miRNA axis. Based on early research from our laboratory, we selected LINC00176 for further exploration. LINC00176 levels were affected by the overexpression and knockdown of Δ40p53. Further, under DNA damage, ER stress, and glucose deprivation, LINC00176 was upregulated in HCT116 p53-/- cells (harboring only Δ40p53) compared to HCT116 p53+/+ cells. Additionally, ChIP and RNA stability assays revealed that Δ40p53 transactivates LINC00176 transcriptionally and stabilizes it post-transcriptionally. We ectopically overexpressed and knocked down LINC00176 in HCT116 p53-/- cells, which affected proliferation, cell viability, and the expression of epithelial markers. Finally, RNA pulldown revealed that LINC00176 sequesters several putative miRNA targets. These results provide important insights into the pivotal role of Δ40p53 in regulating the lncRNA-miRNA axis.

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Section: Introductionmentioning

confidence: 73%

Section: Deciphering the Mechanism Of Action Of Linc00176mentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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The “LINC” in between Δ40p53-miRNA axis in the regulation of cellular homeostasis

Pal

2022

Preprint

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“…To date, many biological functions involving p53 isoforms have been described and, depending on the cell/tissue and origin/type (e.g., malignant/nonmalignant, human/mouse/zebrafish, skin/colon/lung/prostate/breast/brain, etc. ), they include cell-cycle regulation [11,19,90,99,120,[166][167][168][169][170], apoptosis [11,91,120,[170][171][172][173][174][175][176], senescence [19,27,[165][166][167]177,178], DNA repair [167,176,[178][179][180], pluripotent and embryonic stem-cell regulation and cancer stemness [171,[181][182][183], normal and cancer cell metabolism [109,184,185], autophagy [186], proliferation [99,175,[187][188][189][190], cellular invasion, ...…”

Section: Biological Activity and Functions Of The P53 Isoformsmentioning

confidence: 99%

“…Among the few papers tackling the role of p53 isoforms in colorectal cancer, Katoch and colleagues showed that ∆40p53 downregulates the expression of the transcriptional repressor protein YY1 via upregulating miR-186 which consequently inhibits cell pro-liferation of HCT116 −/− cells [187]. There is also evidence of ∆40p53's involvement in autophagy in the ∆40p53 ectopically expressing HCT116 cells.…”

Section: Involvement Of the P53/p73 Isoforms In Crc Development And Progressionmentioning

confidence: 99%

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Horvat

Tadijan

Vlašić

et al. 2021

Cancers

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The p53 tumor suppressor protein is crucial for cell growth control and the maintenance of genomic stability. Later discovered, p63 and p73 share structural and functional similarity with p53. To understand the p53 pathways more profoundly, all family members should be considered. Each family member possesses two promoters and alternative translation initiation sites, and they undergo alternative splicing, generating multiple isoforms. The resulting isoforms have important roles in carcinogenesis, while their expression is dysregulated in several human tumors including colorectal carcinoma, which makes them potential targets in cancer treatment. Their activities arise, at least in part, from the ability to form tetramers that bind to specific DNA sequences and activate the transcription of target genes. In this review, we summarize the current understanding of the biological activities and regulation of the p53/p73 isoforms, highlighting their role in colorectal tumorigenesis. The analysis of the expression patterns of the p53/p73 isoforms in human cancers provides an important step in the improvement of cancer therapy. Furthermore, the interactions among the p53 family members which could modulate normal functions of the canonical p53 in tumor tissue are described. Lastly, we emphasize the importance of clinical studies to assess the significance of combining the deregulation of different members of the p53 family to define the outcome of the disease.

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The “LINC” between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis

Pal

Ghosh

2023

Molecular and Cellular Biology

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Regulation of miR-186-YY1 axis by the p53 translational isoform ∆40p53: implications in cell proliferation

Cited by 4 publications

References 30 publications

The “LINC” in between Δ40p53-miRNA axis in the regulation of cellular homeostasis

The “LINC” in between Δ40p53-miRNA axis in the regulation of cellular homeostasis

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

The “LINC” between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis

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