LncRNA DNM1P35 sponges hsa-mir-326 to promote ovarian cancer progression

Sep 21, 2026

Uploaded by Theodora

LncRNA DNM1P35 is reported to be elevated in ovarian tumors compared with normal tissues and to drive malignant phenotypes in SK-OV-3 and OVCAR-3 cells, including proliferation, migration, and invasion. Mechanistic work identifies microRNA-326 (miR-326) as a downstream target of DNM1P35, where miR-326 overexpression suppresses DNM1P35 tumor-promoting activity by reducing ZEB1 expression and EMT characteristics. In vivo xenograft models show that higher DNM1P35 levels correlate with shorter survival and increased tumor burden, with elevated Ki67 and ZEB1.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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Introduction

Background on lncRNAs and ovarian cancer

Materials and methods

Cell culture

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN LncRNA DNM1P35 sponges hsamir-326 to promote ovarian cancer progression Mei Shen1,3, Yun Mao2,3, Xiaoshi Wang1, Jinsong Huang1, Qingsong Zhang1 & Jinwei Zhang1􀀍 Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in cancer progression. We found lncRNA DNM1P35 is elevated in ovarian tumors compared to normal tissues, and demonstrated that lncRNA DNM1P35 promoted cancer cell proliferation, migration and invasion in SK-OV-3 and OVCAR-3 cell lines. Furthermore, lncRNA DNM1P35 also facilitated the epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Mechanistic studies identified microRNA-326 (miR-326) as a target of lncRNA DNM1P35. Overexpression of miR-326 diminished the tumor-promoting activity of lncRNA DNM1P35, resulting in reduction of Zinc finger E-box-binding homeobox 1 (ZEB1) expression and EMT features. We further revealed that ZEB1, a master transcription factor for EMT that is negatively regulated by miR-326, was essential for lncRNA DNM1P35-mediated cancer cell progression and EMT. Loss of ZEB1 led to compromised pro-tumoral activity of lncRNA DNM1P35 . In vivo studies using a xenograft mouse model of ovarian cancer revealed that tumors with higher levels of lncRNA DNM1P35 led to shorter survival, increased tumor burden, as well as elevated expression of proliferative marker Ki67 and EMT marker ZEB1. Our comprehensive study underscored the significance of lncRNA DNM1P35 in ovarian cancer progression, elucidating the underlying mechanism through miR-326/ZEB1 axis to promote ovarian cancer progression. Keywords Ovarian cancer, lncRNA DNM1P35, miR-326, Epithelial-mesenchymal transition, Gene regulation Ovarian cancer (OC) is one of the most lethal gynecologic malignancies worldwide1. Ovarian cancer exhibits varying trends in terms of the incidence, mortality, and survival rates. Studies have shown a decline in the overall incidence and mortality rates of ovarian cancer, primarily driven by the epithelial histology2,3. The ageadjusted incidence of epithelial ovarian carcinoma differs among races, with white patients having the highest rates4. Survival rates for ovarian cancer patients in Asia after 1, 3, and 5 years were reported as 73.65%, 61.31%, and 59.60% respectively5. Notably, the incidence-based mortality of specific ovarian epithelial cancer deaths has shown a decreasing trend from 2005 to 20186. Standard treatments involve cytoreductive surgery and platinum-based chemotherapy, with relapse being common in advanced cases7. Recent advancements included maintenance therapies like Poly (ADP-ribose) polymerase (PARP) inhibitors for homologous recombination repair-deficient tumors, improving progression-free survival8. Research highlighted breakthroughs in PARP inhibitors’ impact on overall survival. Given these challenges and advancements, there is an urgent need fora deeper understanding of the molecular mechanisms underlying ovarian cancer and the development of innovative diagnostic and therapeutic approaches. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of the human genome’s epigenetic status9. Transcending the traditional understanding of the genome, these non-protein coding transcripts, longer than 200 nucleotides, have been found to play crucial roles in various cellular processes10. Their interactions with other cellular macromolecules, including DNA, RNA, and proteins, drive many essential cancer phenotypes11. The dysregulation of lncRNAs has been associated with tumorigenesis, metastasis, and therapy resistance. For instance, the lncRNA small nucleolar RNA host gene 6 (SNHG6) has been reported to have an oncogenic role in multiple cancers, including colorectal cancer, by activating the Transforming growth factor beta (TGF-β)/ 1Department of Gynaecology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University/Wuxi Medical Center, Nanjing Medical University/Wuxi

FAQs

How does lncRNA DNM1P35 affect ovarian cancer cell behavior?

LncRNA DNM1P35 promotes ovarian cancer cell proliferation, migration, and invasion in SK-OV-3 and OVCAR-3 cell lines. It also facilitates epithelial-mesenchymal transition (EMT).

What role does miR-326 play in the DNM1P35 mechanism?

MicroRNA-326 (miR-326) is identified as a target of lncRNA DNM1P35. Overexpressing miR-326 reduces the tumor-promoting effects of DNM1P35 by lowering ZEB1 and EMT features.

What do the xenograft mouse studies show about DNM1P35?

Xenograft tumors with higher lncRNA DNM1P35 show shorter survival and increased tumor burden. These tumors also exhibit higher Ki67 and ZEB1 expression.

Sep 21, 2026

Uploaded by Theodora