Identification of Long Noncoding RNAs Downregulated Specifically in Ovarian High-grade Serous Carcinoma

Overview

Journal Reprod Med Biol

Specialty Biology

Date 2024 Apr 4

PMID 38571514

Authors

Maki Hayashi-Okada

Shun Sato

Kengo Nakashima

Takahiro Sakai

Tetsuro Tamehisa

Takuya Kajimura

Isao Tamura

Kotaro Sueoka

Norihiro Sugino

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate whether long noncoding RNAs (lncRNAs) are involved in the development or malignant behavior of ovarian high-grade serous carcinoma (HGSC), we attempted to identify lncRNAs specific to HGSC.

Methods: Total RNAs were isolated from HGSC, normal ovarian, and fallopian tube tissue samples and were subjected to a PCR array that can analyze 84 cancer-associated lncRNAs. The lncRNAs that were upregulated and downregulated in HGSC in comparison to multiple samples of normal ovary and fallopian tube were validated by real-time RT-PCR. To infer the function, ovarian cancer cell lines that overexpress the identified lncRNAs were established, and the activation of cell proliferation, migration, and invasion was analyzed.

Results: Eleven lncRNAs (ACTA2-AS1, ADAMTS9-AS2, CBR3-AS1, HAND2-AS1, IPW, LINC00312, LINC00887, MEG3, NBR2, TSIX, and XIST) were downregulated in HGSC samples. We established the cell lines that overexpress ADAMTS9-AS2, CBR3-AS1, or NBR2. In cell lines overexpressing ADAMTS9-AS2, cell proliferation was suppressed, but migration and invasion were promoted. In cell lines overexpressing CBR3-AS1 or NBR2, cell migration tended to be promoted, although cell proliferation and invasion were unchanged.

Conclusion: We identified eleven lncRNAs that were specifically downregulated in HGSC. Of these, CBR3-AS1, NBR2, and ADAMTS9-AS2 had unique functions in the malignant behaviors of HGSC.

Citing Articles

Establishment of a 3D spheroid culture system to evaluate the responsiveness of uterine leiomyoma cells to female hormones.

Sakai T, Sato S, Tamehisa T, Takasaki H, Kajimura T, Tamura I Reprod Med Biol. 2025; 24(1):e12627.

PMID: 39845479 PMC: 11751880. DOI: 10.1002/rmb2.12627.

Diagnostic role of circulating long non-coding RNA LINC00312 in patients with non-small cell lung cancer: a retrospective study.

Zhang R, Jiang Y, Gu J, Zhang X, Xie Y BMC Cancer. 2025; 25(1):47.

PMID: 39789501 PMC: 11721336. DOI: 10.1186/s12885-024-13393-1.

Identification of long noncoding RNAs downregulated specifically in ovarian high-grade serous carcinoma.

Hayashi-Okada M, Sato S, Nakashima K, Sakai T, Tamehisa T, Kajimura T Reprod Med Biol. 2024; 23(1):e12572.

PMID: 38571514 PMC: 10988898. DOI: 10.1002/rmb2.12572.

References

Song E, Xing L, Wang L, Song W, Li D, Wang Y . LncRNA ADAMTS9-AS2 inhibits cell proliferation and decreases chemoresistance in clear cell renal cell carcinoma via the miR-27a-3p/FOXO1 axis. Aging (Albany NY). 2019; 11(15):5705-5725. PMC: 6710069. DOI: 10.18632/aging.102154. View

Hua J, Ahmed M, Guo H, Zhang Y, Chen S, Soares F . Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19. Cell. 2018; 174(3):564-575.e18. DOI: 10.1016/j.cell.2018.06.014. View

. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474(7353):609-15. PMC: 3163504. DOI: 10.1038/nature10166. View

Taylor D, Chu E, Spektor R, Soloway P . Long non-coding RNA regulation of reproduction and development. Mol Reprod Dev. 2015; 82(12):932-56. PMC: 4762656. DOI: 10.1002/mrd.22581. View

Li Y, Wan Q, Wang W, Mai L, Sha L, Mashrah M . LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis. Biomed Pharmacother. 2019; 112:108719. DOI: 10.1016/j.biopha.2019.108719. View

Shen L, Liu W, Cui J, Li J, Li C . Analysis of long non-coding RNA expression profiles in ovarian cancer. Oncol Lett. 2017; 14(2):1526-1530. PMC: 5529754. DOI: 10.3892/ol.2017.6283. View

Zhu C, He X, Chen K, Huang Z, Yao A, Tian X . LncRNA NBR2 aggravates hepatoblastoma cell malignancy and promotes cell proliferation under glucose starvation through the miR-22/TCF7 axis. Cell Cycle. 2021; 20(5-6):575-590. PMC: 8018347. DOI: 10.1080/15384101.2021.1885236. View

Cui Z, Ren S, Lu J, Wang F, Xu W, Sun Y . The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol. 2012; 31(7):1117-23. DOI: 10.1016/j.urolonc.2011.11.030. View

Wang A, Jin C, Li H, Qin Q, Li L . LncRNA ADAMTS9-AS2 regulates ovarian cancer progression by targeting miR-182-5p/FOXF2 signaling pathway. Int J Biol Macromol. 2018; 120(Pt B):1705-1713. DOI: 10.1016/j.ijbiomac.2018.09.179. View

10.

Tao P, Yang B, Zhang H, Sun L, Wang Y, Zheng W . The overexpression of lncRNA MEG3 inhibits cell viability and invasion and promotes apoptosis in ovarian cancer by sponging miR-205-5p. Int J Clin Exp Pathol. 2020; 13(5):869-879. PMC: 7270692. View

11.

Yang W, Zheng Z, Yi P, Wang S, Zhang N, Ming J . LncRNA NBR2 Inhibits the Malignancy of Thyroid Cancer, Associated With Enhancing the AMPK Signaling. Front Oncol. 2020; 10:956. PMC: 7304297. DOI: 10.3389/fonc.2020.00956. View

12.

Bhardwaj J, Paliwal A, Saraf P, Sachdeva S . Role of autophagy in follicular development and maintenance of primordial follicular pool in the ovary. J Cell Physiol. 2021; 237(2):1157-1170. DOI: 10.1002/jcp.30613. View

13.

Sulewska A, Niklinski J, Charkiewicz R, Karabowicz P, Biecek P, Baniecki H . A Signature of 14 Long Non-Coding RNAs (lncRNAs) as a Step towards Precision Diagnosis for NSCLC. Cancers (Basel). 2022; 14(2). PMC: 8773641. DOI: 10.3390/cancers14020439. View

14.

Li H, Huang H, Li S, Mei H, Cao T, Lu Q . Long non-coding RNA ADAMTS9-AS2 inhibits liver cancer cell proliferation, migration and invasion. Exp Ther Med. 2021; 21(6):559. PMC: 8027749. DOI: 10.3892/etm.2021.9991. View

15.

Xie L, Cui G, Li T . Long Noncoding RNA CBR3-AS1 Promotes Stem-like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p. J Oncol. 2022; 2022:2260211. PMC: 9019443. DOI: 10.1155/2022/2260211. View

16.

Cardillo N, Russo D, Newtson A, Reyes H, Lyons Y, Devor E . Identification of Novel lncRNAs in Ovarian Cancer and Their Impact on Overall Survival. Int J Mol Sci. 2021; 22(3). PMC: 7865736. DOI: 10.3390/ijms22031079. View

17.

Sato S, Maekawa R, Tamura I, Shirafuta Y, Shinagawa M, Asada H . SATB2 and NGR1: potential upstream regulatory factors in uterine leiomyomas. J Assist Reprod Genet. 2019; 36(11):2385-2397. PMC: 6885490. DOI: 10.1007/s10815-019-01582-y. View

18.

He L, Xiao Y, Ma L, Zhao F, Yu T, Huang Y . ADAMTS9-AS2: a potential diagnostic and prognostic hallmark in prostate cancer. J BUON. 2021; 26(4):1623-1627. View

19.

Huarte M, Guttman M, Feldser D, Garber M, Koziol M, Kenzelmann-Broz D . A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010; 142(3):409-19. PMC: 2956184. DOI: 10.1016/j.cell.2010.06.040. View

20.

Takahashi K, Podyma-Inoue K, Saito M, Sakakitani S, Sugauchi A, Iida K . TGF-β generates a population of cancer cells residing in G1 phase with high motility and metastatic potential via KRTAP2-3. Cell Rep. 2022; 40(13):111411. DOI: 10.1016/j.celrep.2022.111411. View