Cervical cancer (CC), as a common female malignant tumor in the world, is an important risk factor endangering the health of women all over the world, especially one of the main problems of reproductive health of women in developing countries [1]. On November 17, 2020, the World Health Organization (WHO) launched the “Global Strategy to Accelerate the Elimination of Cervical Cancer”, aiming to eradicate cervical cancer as soon as possible on a global scale through a combination of prevention and treatment, highlighting the significance and urgency of cervical cancer treatment [2]. According to previous WHO data, about 90 % of the 270,000 cervical cancer deaths worldwide in 2015 occurred in low- and middle-income countries, and the mortality rate was about 18 times that of developed countries [3]. Although important progress has been made in cervical cancer prevention, screening, diagnosis and treatment in the past decade, CC still plagues the health of women around the world due to radiotherapy resistance and tumor metastasis [4]. Therefore, in-depth study of the mechanism of tumor occurrence and metastasis to find new targeted therapy is an important measure for CC treatment.
Long non-coding RNA (lncRNA) is a class of RNA molecules greater than 200 nt in length, which do not encode proteins themselves. However, recent studies have shown that lncRNAs can regulate gene expression at multiple levels (epigenetic, transcriptional, and post-transcriptional regulation, etc.), and are involved in the pathological process of many diseases, especially in malignant tumors, involved in the occurrence and development of tumors [5,6]. LncRNA HEIH is located on chromosome 5 and is a member of the lncRNA family, which was first identified and studied in hepatocellular carcinoma and found to be highly expressed in hepatocellular carcinoma patients [7]. At present, the effect of HEIH in promoting tumor proliferation has been reported in many tumors including liver cancer, gastric cancer and breast cancer [8,9]. To date, more than 170 post-transcriptional modifications have been found in coding and non-coding RNAs, and N6 methyladenine (m6A) is one of the most common and abundant RNA post-transcriptional modifications in eukaryotes [10]. Studies have shown that m6A is involved in various aspects of RNA metabolism, including pre-mRNA splicing, 3′ end processing, nuclear export, translation regulation, mRNA decay, and noncoding RNA processing, thereby affecting mammalian embryonic development, neural development, metabolism, circadian Rhythm, stress response and the development of cancer [[11], [12], [13], [14]]. As one of RNA methyltransferases, RBM15 has been reported to be involved in tumor regulation [15]. However, its role in lncRNA stability remains unclear.
Cancer stem cells (CSCs) are a class of cells with self-renewal and differentiation ability, which are involved in the occurrence, metastasis and recurrence of tumors [16]. Current studies have shown that CSCs affect tumor chemoradiotherapy tolerance and seriously endanger the prognosis of patients. Epidermal growth factor receptor (EGFR) is a member of the transmembrane tyrosine kinase receptor family and is widely expressed in human cancers. EGFR autophosphorylates upon binding to corresponding ligands and activates downstream signaling pathways that are critical for many processes, including cell proliferation, angiogenesis, and CSCs enrichment [17,18]. However, its stemness and regulatory mechanism in cervical cancer cells are still unclear. This study aimed to investigate the effect of m6A methylation on the stability of lncRNA HEIH and its regulatory mechanism on tumor cell stemness through in vitro and in vivo assays, and to provide theoretical data for the targeted therapy of CC.
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