LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway
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Cancer Cell International Open Access
PRIMARY RESEARCH
LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR‑148a/CDK1 pathway Chen Wang1†, Shiqing Shao1*† , Li Deng2, Shelian Wang1 and Yongyan Zhang1
Abstract Background: Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) regulates the radiosensitivity of CC remains unknown. Methods: Quantitative real-time polymerase chain reaction was used to measure the expression levels of SNHG12 and microRNA-148a (miR-148a). The radiosensitivity of cells was evaluated by clonogenic assay. Flow cytometry and caspase-3 activity assay were performed to assess the apoptosis ability and cell cycle distribution of cells. Besides, dual-luciferase reporter and RNA immunoprecipitation assay were used to verify the interaction between miR-148a and SNHG12 or cyclin-dependent kinase 1 (CDK1). Also, the protein levels of CDK1, CCND1 and γ-H2AX were detected by western blot analysis. Furthermore, in vivo experiments were conducted to verify the effect of SNHG12 on CC tumor growth. Ki-67 and TUNEL staining were employed to evaluate the proliferation and apoptosis rates in vivo. The hematoxylin and eosin (HE) staining were employed to evaluate the tumor cell morphology. Results: SNHG12 was upregulated in CC tissues and cells, and its knockdown improved the radiosensitivity by promoting the radiation-induced apoptosis and cell cycle arrest of CC cells. Also, miR-148a could be sponged by SNHG12 and could target CDK1. MiR-148a inhibitor or CDK1 overexpression could invert the promotion effect of silencedSNHG12 on CC radiosensitivity. Meanwhile, SNHG12 interference reduced the tumor growth of CC, increased miR148a expression, and inhibited CDK1 level in vivo. Conclusion: LncRNA SNHG12 promoted CDK1 expression to regulate the sensitivity of CC cells to radiation through sponging miR-148a, indicating that SNHG12 could be used as a potential biomarker to treat the radiotherapy resistance of CC patients. Keywords: Cervical cancer, Radiosensitivity, SNHG12, miR-148a, CDK1 Background Cervical cancer (CC) is one of the most common malignant tumors in women, which poses a severe threat to women’s health [1, 2]. CC can be eliminated through
*Correspondence: [email protected] † Chen Wang and Shiqing Shao contributed equally to this work 1 Department of Obstetrics and Gynecology, Huaihe Hospital of Henan University, No.8 Baogonghu North Road, Kaifeng 475000, Henan, China Full list of author information is available at the end of the article
early prevention and treatment, and radiotherapy is the main mean of CC treatment [3, 4]. However, the emergence of radiotherapy resistance seriously hinders the treatment process of CC, resulting in poor efficacy of CC patients [5, 6]. Thus, it is particularly important to search for biomarkers related to radiosensi
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