PODN and PODNL1: Emerging Target Genes with Potential Value in Disease Research
With advances in precision medicine and functional genomics, a growing number of noncanonical cancer-associated genes are entering the research spotlight. PODN (Podocan) and its homolog PODNL1 (Podocan-like protein 1), members of a leucine-rich repeat (LRR)-associated protein family, have recently received attention in cancer progression, immune regulation, and vascular disease research.
Over the past two years, several studies have reported potential roles for PODN in the immune microenvironment of triple-negative breast cancer (TNBC) and in papillary thyroid carcinoma (PTC). PODNL1 has also been implicated in HIV-associated pulmonary vascular disease (HIV-PVD), opening new directions for investigating the biological functions and disease associations of the PODN family.
01
PODN Is Associated with Tumor Immune Regulation and Patient Prognosis
TNBC is a breast cancer subtype lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. It is characterized by high aggressiveness, a substantial risk of recurrence, and limited treatment options.
As immunotherapy advances, TNBC research is shifting from a sole focus on tumor cells toward the tumor immune microenvironment and its relationship with treatment response. However, because this microenvironment is highly complex, accurately predicting prognosis and therapeutic response remains an important research priority.
A study published in Frontiers in Immunology in April 2026 used bioinformatics to identify genes associated with T cell-mediated tumor killing and to construct a prognostic risk model for patients with TNBC.
PODN, together with SEMA7A, GPR34, and COCH, formed a four-gene prognostic model. PODN expression was associated with TNBC risk stratification, immune microenvironment features, and potential treatment response.
Further analyses identified differences between risk groups in immune checkpoint expression, immune cell infiltration, and drug sensitivity. These findings suggest that PODN expression may be associated with features of the tumor immune microenvironment and may warrant further investigation as a prognostic biomarker.
It is important to note that the study was based primarily on public datasets and bioinformatic analyses. It identified associations between PODN expression and disease characteristics, while the underlying molecular mechanisms require further experimental validation.
02
m6A Modification Reveals a New Mechanism Regulating PODN in Thyroid Cancer
Beyond breast cancer, the role of PODN in PTC has also attracted research interest.
A study published online in Biochemical Genetics in July 2025 found that the RNA epigenetic regulator METTL3 modulates PODN expression through m6A RNA methylation and affects malignant behaviors in PTC cells.
The study showed that:
· METTL3 promotes m6A modification of PODN mRNA;
· The m6A reader protein IGF2BP1 helps maintain PODN mRNA stability;
· Increased PODN expression inhibits PTC cell proliferation, migration, and invasion.
The investigators also found that enhanced PODN expression increased the sensitivity of PTC cells to sorafenib. In vitro, the combination produced stronger antitumor effects.
This study revealed a new mechanism through which RNA epigenetic regulation controls PODN expression.
METTL3-mediated m6A modification influences PODN mRNA stability and, by regulating PODN expression, affects the proliferation, migration, and invasion of papillary thyroid carcinoma cells. The findings suggest that strategies centered on PODN regulation may offer a new direction for PTC research.
03
PODNL1 May Participate in HIV-Associated Pulmonary Vascular Disease
In addition to PODN, PODNL1, another member of the PODN family, has recently shown new disease associations.
A conference abstract published in Physiology in May 2026 reported a potential mechanism involved in HIV-PVD.
The report indicated that PODNL1 expression was elevated in HIV-associated models and may participate in pulmonary vascular remodeling.
Further experiments showed that:
· The HIV-associated factor Tat induced increased PODNL1 expression;
· PODNL1 overexpression promoted collagen I expression in pulmonary artery smooth muscle cells;
· Elevated PODNL1 was associated with increased markers of cell proliferation.
The investigators proposed that the HIV-Tat/PODNL1 signaling axis may contribute to HIV-associated pulmonary vascular disease, identifying a candidate regulator for further mechanistic research. Because the available evidence is primarily from a conference abstract, additional full studies and independent experimental validation are needed.
04
PODN Family Research Supports Disease-Mechanism Discovery and Precision Medicine
From tumor immune regulation and drug-sensitivity research to pulmonary vascular disease, PODN and PODNL1 are not yet established therapeutic targets. Nevertheless, their potential associations with diverse disease phenotypes are receiving increasing attention, illustrating the value of functional genomics in identifying candidate mechanisms and therapeutic strategies.
Future studies integrating gene editing, functional validation, and drug screening may clarify how PODN family members contribute to disease development and support the discovery of new precision-treatment strategies.
EDITGENE has established multiple in-stock PODN gene-edited cell models. Selected products are listed below:
| Catalog | Product | Gene | Order Now |
|---|
| EDJ-KQ58208 | PODN Knockout HeLa Cell Line | PODN | Order Now |
| EDJ-KQ66698 | PODN Knockout A-549 Cell Line | PODN | Order Now |
| EDJ-KQ75111 | PODN Knockout HCT116 Cell Line | PODN | Order Now |
| EDJ-KQ9043 | PODN Knockout HEK293 Cell Line | PODN | Order Now |
Beyond the in-stock products listed above, EDITGENE provides custom Knockout, Knock-in, and Point-mutation cell model development tailored to specific research needs. Our end-to-end workflow covers feasibility assessment, sgRNA design and editing, monoclonal screening, and genotype validation, supporting gene-function studies, target-mechanism research, and in vitro evaluation of candidate therapies.
References
[1] Sun Y, Sun B, Yang M, Deng Q. m6A Methylation of PODN Regulated by METTL3 Synergizes with Sorafenib to Exhibit Antitumor Function in Papillary Thyroid Cancer. Biochemical Genetics, 2026, 64(3):3433-3450. DOI:10.1007/s10528-025-11201-4.
[2] Zhang C, Hu Y, Han Y, et al. Comprehensive analysis of prognostic characteristics based on T cell-mediated tumor killing related genes in triple negative breast cancer. Frontiers in Immunology, 2026, 17:1801004. DOI:10.3389/fimmu.2026.1801004.
[3] Kovacs L, Kress TC, Kasa A, et al. Podnl1 as a novel mediator of HIV-associated pulmonary vascular disease. Physiology, 2026, 41(S1):2299568. DOI:10.1152/physiol.2026.41.S1.2299568.
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