LncRNA ABHD11-AS1 Participates in the Progression of Cervical Carcinoma by Targeting miR-1254 and Is the Key to the Diagnosis and Treatment of Cervical Carcinoma in the Future

Abstract

Cervical carcinoma is the most common gynecologic tumor in the clinic. The incidence of cervical carcinoma has been increasing in recent years, and the age of the affected population is showing a younger trend. Long-chain noncoding RNA (LncRNA) acts in the cell cycle. In cervical carcinoma, many studies have also confirmed the important role of LncRNA. LncRNA ABHD11-AS1 is one of the genes abnormally expressed in cervical carcinoma, but the specific situation has not been fully explained. This study intended to confirm whether LncRNA ABHD11-AS1 can be applied for the treatment of cervical carcinoma in the future. From January 2015 to January 2017, 72 cases of cervical carcinoma patients and 78 cases of healthy people during the same period in our hospital were selected for prospective analysis. ABHD11-AS1 and miR-1254 in serum and carcinoma tissues of cervical carcinoma patients were detected. In addition, human cervical carcinoma cells HeLa and CaSki were obtained to analyze the effects of interference with ABHD11-AS1 and miR-1254 on the biological behavior of cervical carcinoma cells. Finally, the correlation of ABHD11-AS1 with miR-1254 was verified by double fluorescein reporter enzyme and immunocoprecipitation. ABHD11-AS1 was upregulated, and miR-1254 was reduced in serum and carcinoma tissues of cervical carcinoma patients (P < 0.05). The expression levels of the two were negatively correlated (P < 0.001). ABHD11-AS1 decreased and miR-1254 increased in serum of cervical carcinoma patients after treatment (P < 0.05). High ABHD11-AS1 and low miR-1254 had a close correlation with the poor prognosis of cervical carcinoma patients (P < 0.05). Silencing LncRNA ABHD11-AS1 could inhibit the activity of cervical carcinoma cells (P < 0.05), while inhibiting miR-1254 could promote the activity of cervical carcinoma cells (P < 0.05). ENCORI online website found that LncRNA ABHD11-AS1 and miR-1254 had binding sites. Bifluorescein reporter enzyme experiment found that ABHD11-AS1-WT fluorescence activity was inhibited by transfected miR-1254-mimics (P < 0.05). LncRNA ABHD11-AS1 accelerates proliferation, invasion, and migration of cervical carcinoma cells through targeted regulation of miR-1254, which may become the key to the treatment of cervical carcinoma.

Figure 1

Expression of LncRNA ABHD11-AS1 and miR-1254 in cervical carcinoma. ^∗P < 0.05. (a) Comparison of the expression level of LncRNA ABHD11-AS1 in serum of cervical carcinoma patients and healthy people. (b) Comparison of miR-1254 expression level in serum of cervical carcinoma patients and healthy people. (c) Comparison of expression levels of LncRNA ABHD11-AS1 in carcinoma tissues and adjacent tissues of cervical carcinoma patients. (d) Comparison of miR-1254 expression levels in carcinoma tissues and adjacent tissues of cervical carcinoma patients. (e) Correlation analysis of LncRNA ABHD11-AS1 and miR-1254 in serum of cervical carcinoma patients. r = −0.517; P < 0.001. (f) Correlation analysis of LncRNA ABHD11-AS1 and miR-1254 in carcinoma tissues of cervical carcinoma patients. r = −0.691; P < 0.001.

Figure 2

Clinical significance of LncRNA ABHD11-AS1 and miR-1254 in cervical carcinoma. ^∗P < 0.05. ^∗∗∗P < 0.001. (a) Comparison of expression levels of LncRNA ABHD11-AS1 in serum of cervical carcinoma patients before and after treatment. (b) Comparison of miR-1254 expression level in serum of cervical carcinoma patients before and after treatment. (c) Comparison of expression levels of LncRNA ABHD11-AS1 between patients with prognosis death and patients with survival. (d) Comparison of miR-1254 expression level between patients with prognosis death and patients with survival. (e) Predictive value of LncRNA ABHD11-AS1 for prognosis and death of cervical carcinoma patients. AUC: 0.904; 95% CI: 0.801–1.0; cutoff: 6.275; sensitivity: 88.89%; specificity: 90.00%; P < 0.001. (f) Predictive value of miR-1254 for prognosis and death of cervical carcinoma patients. AUC: 0.907; 95% CI: 0.800–1.015; cutoff: 3.095; sensitivity: 88.89%; specificity: 83.33%; P < 0.001. (g) Three-year survival curve of patients in group A and group B. (h) Three-year survival curve of patients in group C and group D.

Figure 3

Effect of LncRNA ABHD11-AS1 on cervical carcinoma cells. ^∗P < 0.05. ^∗∗∗P < 0.001. ^#Compared with the ABHD11-AS1-sh group, P < 0.05. ^&Compared with the ABHD11-AS1-si group, P < 0.05. (a) Comparison of expression levels of LncRNA ABHD11-AS1 in HeLa, CaSki, and HcerEpic. (b) qRT-PCR verified the success rate of cell transfection. (c) HeLa cell proliferation curve. (d) CaSki cell proliferation curve. (e) Invasion of HeLa and CaSki cells. (f) HeLa and CaSki cell migration. (g) Apoptosis rate of HeLa and CaSki cells.

Figure 4

Effect of miR-1254 on cervical carcinoma cells. ^∗P < 0.05; ^∗∗∗P < 0.001. ^#Compared with the miR-1254-mimics group, P < 0.05. ^&Compared with the miR-1254-inhibition group, P < 0.05. (a) Comparison of miR-1254 expression levels in HeLa, CaSki, and HcerEpic. (b) qRT-PCR verified the success rate of cell transfection. (c) HeLa cell proliferation curve. (d) CaSki cell proliferation curve. (e) Invasion of HeLa and CaSki cells. (f) HeLa and CaSki cell migration. (g) Apoptosis rate of HeLa and CaSki cells.

Figure 5

Verification of targeted relationship between LncRNA ABHD11-AS1 and miR-1254. ^∗P < 0.05. ^#Compared with the ABHD11-AS1-sh group, P < 0.05. ^&Compared with the ABHD11-AS1-si group, P < 0.05. (a) ENCORI analysis of the binding sites of LncRNA ABHD11-AS1 and miR-1254. (b) Detection of fluorescence activity of bifluorescein reporter enzyme. (c) Immune coprecipitation test results. (d) Expression level of miR-1254 in cervical carcinoma cells transfected with ABHD11-AS1-sh, ABHD11-AS1-si, and ABHD11-AS1-NC.