Journal of Zhejiang University

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Hypoxia promotes ovarian cancer progression via Lnc-DARS-AS1/miR-378a-5p/SLC2A12 axis

Author(s): Wenjie ZENG^1, ^2, ^3, ⁴, Hubin XU⁵, Huafeng SHOU^2, ^3, ⁴, Haimin JIANG⁵, Mengyu ZHANG⁵, Xiaoyan CHEN², Weiguo LU^1, ^6, ⁷
Affiliation(s): ¹Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China ²Center for Reproductive Medicine, Department of Gynecology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China ³Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou 310014, China ⁴Clinical Research Center for Cancer of Zhejiang Province, Hangzhou 310014, China ⁵The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou 311121, China ⁶Zhejiang Key Laboratory of Maternal and Infant Health, Hangzhou 310006, China ⁷Zhejiang Provincial Clinical Research Center for Gynecological Diseases, Hangzhou 310006, China
Corresponding email(s): Weiguo LU, lbwg@zju.edu.cn
Key Words: Hypoxia; Ovarian cancer; Long non-coding RNA DARS-AS1; miR-378a-5p; Solute carrier family 2 member 12; RNA sequencing

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Wenjie ZENG^1,^2,^3,⁴, Hubin XU⁵, Huafeng SHOU^2,^3,⁴, Haimin JIANG⁵, Mengyu ZHANG⁵, Xiaoyan CHEN², Weiguo LU^1,^6,⁷. Hypoxia promotes ovarian cancer progression via Lnc-DARS-AS1/miR-378a-5p/SLC2A12 axis[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500083

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Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: To examine hypoxia-induced alterations in ovarian cancer and elucidate the underlying molecular mechanisms mediated by long non-coding RNAs (lncRNAs). Transwell and MTT assays were performed to assess the migration, invasion and proliferative abilities of ovarian cancer cells. Western blot analysis was conducted to evaluate the expression of factors associated with epithelial-mesenchymal transition (EMT). RNA sequencing was carried out to identify potential targets, and dual-luciferase and biotin-labeled miRNA pull-down assays were performed to identify interactions between these targets. Gain- and loss-of-function experiments were conducted to validate their effects. Hypoxia promoted the migration, invasion, proliferation, and EMT of HO8910 and A2780 cells. Under hypoxic conditions, the expression of Lnc-DARS-AS1 was significantly increased, and this upregulation exerted a proliferative effect on ovarian cancer cells. Furthermore, Lnc-DARS-AS1 promoted solute carrier family 2 member 12 (SLC2A12) expression, accelerating ovarian cancer progression. Luciferase, biotin-labeled miRNA pull-down, and cellular function assays confirmed that Lnc-DARS-AS1 binds to miR-378a-5p to enhance SLC2A12 levels. The expression levels of SLC2A12 were determined in samples from patients with ovarian cancer, and they showed a positive correlation with cancer progression. This research established that the Lnc-DARS-AS1/miR-378a-5p/SLC2A12 axis is involved in ovarian cancer progression under hypoxic conditions, providing new perspectives on the treatment and management of ovarian cancer.

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On-line Access: 2025-12-15

Received: 2025-02-19

Revision Accepted: 2025-11-04

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Citations: Bibtex RefMan EndNote GB/T7714

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