The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

Zhang, Qun; Zhu, Yazhi; Cao, Xinyu; Tan, Winston; Yu, Juebang; Lü, Yaqiong; Kang, Ran; Wang, Xiaolan; Li, Ermao

doi:10.1186/s12943-023-01749-3

Cited by 29 publications

(14 citation statements)

References 134 publications

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“…It has been widely reported that liposome is an ideal platform for fat‐soluble drug loading and slow release. [ 27 ] Hyaluronic acid and gelatin, as the major component of ECM, have proven effective in regulating key cellular processes and behaviors, including proliferation, differentiation, and the inflammatory response, [ 28 ] which may contribute to cellular reprogramming. [ 29 ] Adhesive seed microsphere AFHS with TiT cocktail nucleus and positively charged surface modification were developed through liposome nanodrug carrier system, microfluidic technology, photoresponsive crosslinking technology, and poly allylamine hydrochloride (PAH) activation (Figure 2f).…”

Section: Resultsmentioning

confidence: 99%

Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

Ji,

Li,

Xiang

et al. 2024

Advanced Science

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The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of “seeding and harvest”, are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast‐to‐DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two‐pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

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Section: Resultsmentioning

confidence: 99%

Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

Ji,

Li,

Xiang

et al. 2024

Advanced Science

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“…Recent research into piRNA dysregulation across various cancers has highlighted its in uential role in facilitating tumor cell growth, proliferation, metastasis, and progression [21][22][23] . Compared to other noncoding RNAs, piRNAs exhibit superior speci city, deliverability, and tolerability within tumors, which makes them the optimal targets for cancer therapy [51,52] . PiRNAs, with their profound impact on epigenetic regulation, are emerging as pivotal diagnostic markers and therapeutic avenues across a spectrum of malignancies.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway

Ye,

Wu,

et al. 2024

Preprint

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Background: Cancer-associated fibroblasts (CAFs) play a critical role in tumor progression. In this study, we explored the influence of exosomal piR-35462 (piR-35462) derived from CAFs on oral squamous cell carcinoma (OSCC) progression. Methods: CAFs and normal fibroblasts (NFs) were obtained from patients-derived samples of OSCC and adjacent normal tissues. Exosomes extracted from CAFs and NFs were confirmed and piRNAs was identified screened. CCK8 assays, EdU and Transwell assays were performed to assess tumor proliferation and metastasis. A nude mouse model was established to assess the impact of exosomal piR-35462 on tumor progression. Results: CAFs-derived exosomes showed a enhanced piR-35462 expression and promoted OSCC cell proliferation, migration and invasion. Additionally, elevated piR-35462 expression in OSCC tissues correlates with poor prognosis. Mechanistically, CAFs-derived exosomal piR-35462 increased the expression of fat mass and obesity-associated protein (FTO) in OSCC cells. By inhibiting N6-methyladenosine (m6A) RNA methylation, the overexpression of FTO further enhances the stability and expression levels of Twist1 mRNA, thereby contributing to epithelial-mesenchymal transition (EMT) and tumor progression. In vivo xenograft tumor model also confirmed the same results. Conclusion: The achieved outcomes elucidate that CAFs can deliver piR-35462 containing exosomes to OSCC cells and promote OSCC progression via FTO/Twist mediated EMT pathways, and could represent a promising therapeutic target for OSCC.

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“…The genome sequences coding for certain piRNA classes are often found within proteincoding genes, and functional piRNAs are predominantly produced from the 3 -untranslated regions (3 -UTRs) of mRNA during translation [77]. Furthermore, these mRNA 3 -UTRs, which produce piRNAs, often contain transposon sequences whose activity is regulated by these piRNAs at the post-transcriptional level [78].…”

Section: Discussionmentioning

confidence: 99%

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

Timofeeva

Fedorov

Asaturova

et al. 2023

IJMS

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The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.

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The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

Cited by 29 publications

References 134 publications

Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

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