Long Noncoding RNA KCNMB2-AS1 Stabilized by N⁶-Methyladenosine Modification Promotes Cervical Cancer Growth Through Acting as a Competing Endogenous RNA

Abstract

Long noncoding RNA (lncRNA) is emerging as an essential regulator in the development and progression of cancer, including cervical cancer (CC). In this study, we found a CC-related lncRNA, KCNMB2-AS1, which was significantly overexpressed in CC and linked to poor outcomes. Depletion of KCNMB2-AS1 remarkably inhibited CC cell proliferation and induced apoptosis. In vivo xenograft models revealed that knockdown of KCNMB2-AS1 evidently delayed tumor growth. Mechanistically, KCNMB2-AS1 was predominantly located in the cytoplasm and served as a competing endogenous RNA to abundantly sponge miR-130b-5p and miR-4294, resulting in the upregulation of IGF2BP3, a well-documented oncogene in CC. Moreover, IGF2BP3 was able to bind KCNMB2-AS1 by three N6-methyladenosine (m6A) modification sites on KCNMB2-AS1, in which IGF2BP3 acted as an m6A “reader” and stabilized KCNMB2-AS1. Thus, KCNMB2-AS1 and IGF2BP3 formed a positive regulatory circuit that enlarged the tumorigenic effect of KCNMB2-AS1 in CC. Together, our data clearly suggest that KCNMB2-AS1 is a novel oncogenic m6A-modified lncRNA in CC, targeting KCNMB2-AS1 and its related molecules implicate the therapeutic possibility for CC patients.

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

“…97 Besides, m 6 A “reader” IGF2BP family proteins were also reported serving as carcinogenic roles in CVC. 98 , 99 …”

Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1

“…Recently, a substantial amount of research has investigated the roles of lncRNAs in cervical cancer, and satisfactory results have been obtained (28)(29)(30). Several lncRNAs are differentially expressed in cervical cancer, which affect several aggressive properties of the tumour (31).…”

N6-Methyladenosine-Related Long Noncoding RNAs as Potential Prognosis Biomarkers for Endometrial Cancer

“…29 In cervical cancer cells, IGF2BP3 enhances the stability of lnRNA KCNMB2-AS1 by binding to it, thereby promoting tumour cell proliferation. 30 M6A-modified NEAT1-1 can facilitate the development of bone metastasis in prostate cancer cells. Furthermore, the m6A level of NEAT1-1 can be used as a predictor of death in patients with prostate cancer bone metastases.…”