Abstract
The long-term chronic inflammation of cervical intraepithelial neoplasia (CIN) induces the initiation and progression of cervical cancer. Long non-coding RNAs (LncRNAs) are being identified to be involved into inflammation and carcinogenesis and could function as cancer biomarkers in clinical. However, the significance of inflammation-related LncRNA (e.g. LncRNA-IL7R) in cervical cancer is limited. We, here, investigated the clinical role of inflammation-related LncRNA-IL7R (Lnc-IL7R) in healthy cervical tissue (n=15), CIN 1/2/3 (n=35), cervical cancer (n=70), and clarified its function via knockdown in vitro and in vivo. The results showed that the expression of Lnc-IL7R was increased from normal tissues to neoplastic lesions and cervical cancer. Up-regulated Lnc-IL7R positively correlated to tumor size, International Federation of Gynaecology and Obstetrics (FIGO) stage, and lymph node metastasis (LNM). Patients with high expression of Lnc-IL7R had poor prognosis with short overall survival (OS) time, and Cox regression analysis revealed that Lnc-IL7R could be independent prognostic factor for cervical cancer. Moreover, knockdown of Lnc-IL7R by two different siRNAs in cervical cancer cell lines Hela and SiHa induced impaired cell vitality and caspase-3-dependent apoptosis in vitro. Furthermore, inhibition of Lnc-IL7R in vivo significantly restricted the tumor growth with decreased expressions of proliferation index Ki-67 and Lnc-IL7R. These data indicated that Lnc-IL7R predicts a poor clinical outcome of cervical cancer patients, and knockdown of Lnc-IL7R is amenable to the treatment of cervical cancer.
Highlights
Cervical cancer is the major cause of death from gynecological cancers and is the third most common malignancy in women worldwide with a global incidence of 500000 and mortality of 250000
To investigate the expression pattern of Lnc-IL7R in cervical cancer, normal cervix (n=15), (CIN1/2/3) (n=35), and cervical cancer samples (n=70) were collected and the results of Q-PCR indicated that the expression of Lnc-IL7R was increased during the development of cervical cancer
We further analyzed the expression of Lnc-IL7R in different groups, 12 in 15 (80%) of normal cervix showed the low expression of Lnc-IL7R and only 3 in 15 (20%) showed the high expression of Lnc-IL7R
Summary
Cervical cancer is the major cause of death from gynecological cancers and is the third most common malignancy in women worldwide with a global incidence of 500000 and mortality of 250000. More than 85% of these cases and deaths occurred in developing countries, including China [1,2]. Persistent infection with oncogenic subtypes of the human papillomavirus (HPV) results in chronic inflammation, leading to the cervical intraepithelial neoplasia (CIN) and carcinogenesis of uterine cervix [3]. The signs and symptoms of cervical cancer often occur in the later stages of the infection (CIN 1, 2, and 3), the detection of tumorigenesis at the microscopic level is inefficient in earliest stages of diagnosis [4]. Some proteins and HPV DNA-based biomarkers are developed for the diagnosis of cervical cancer in clinical, such as SSC-Ag, CA-125, CEA, and Cytokeratins [4]. It is still urgent to identify new and effective prognostic markers and therapeutic strategies to improve treatment of cervical cancer
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