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Review
. 2021 Jul 22;22(15):7829.
doi: 10.3390/ijms22157829.

LncRNA MORT (ZNF667-AS1) in Cancer-Is There a Possible Role in Gynecological Malignancies?

Riccardo Di Fiore  1   2 , Sherif Suleiman  1 , Rosa Drago-Ferrante  3 , Ana Felix  4 , Sharon A O'Toole  5 , John J O'Leary  6 , Mark P Ward  6 , James Beirne  7 , Angel Yordanov  8 , Mariela Vasileva-Slaveva  9 , Yashwanth Subbannayya  10 , Francesca Pentimalli  11 , Antonio Giordano  2   12 , Jean Calleja-Agius  1
Affiliations
Review

LncRNA MORT (ZNF667-AS1) in Cancer-Is There a Possible Role in Gynecological Malignancies?

Riccardo Di Fiore et al. Int J Mol Sci. .

Abstract

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as 'rare' due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).

Keywords: MORT (ZNF667-AS1); cervical cancer; endometrial cancer; epigenetic therapy; epigenetics; lncRNA-based therapy; long non-coding RNA; ovarian cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MORT (ZNF667-AS1) and ZNF667 genomic location. MORT (ZNF667-AS1) and ZNF667 are head-to-head antisense-sense strands. MORT (ZNF667-AS1) is also located in 19q13.43 (GRCh38p13 database, chr19: 56,477,874-56,495,437; NCBI: NR_036521.1). ZNF667 is also located in 19q13.43 (GRCh38p13 database, chr19: 56,439,329-56,477,345; NCBI: NM_022103.4).
Figure 2
Figure 2
Pathological role of MORT (ZNF667-AS1) in gynecological cancers. Underexpression of MORT (ZNF667-AS1) could promote tumor initiation in ovarian, cervical, and endometrial cancers through different molecular mechanisms not yet well explored. In ovarian cancer, MORT (ZNF667-AS1) downregulation and consequent miR-21 overexpression promote the proliferation of ovarian cancer cells. In cervical cancer, downregulation of MORT (ZNF667-AS1) and consequent overexpression of miR-93-3p reduce the expression of PEG3, thereby allowing cell proliferation and EMT. In endometrial cancer and uterine carcinosarcoma, MORT (ZNF667-AS1) expression is silenced by aberrant DNA methylation. However, its function mechanism in these types of cancer is unknown. BioRender has been used to create parts of this figure. (https://biorender.com, accessed on 18 May 2021).
See this image and copyright information in PMC

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