Wen-Jing Shi1, Hao Liu2, Ya-Fang Ge3, Dan Wu4, Ya-Jing Tan5, Yu-Chen Shen3, Huihui Wang6, Han Xu6. 1. Department of Clinical Laboratory, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030,China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China. 2. Department of Health Technology and Informnatics, Hong Kong Polytechnic University, 999077, Hong Kong Special Administrative Region. 3. Department of Clinical Laboratory, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030,China. 4. Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China. Electronic address: wudanint@yeah.net. 5. Center of Reproductive Medicine, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 6. Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Abstract
BACKGROUND: Recent studies have indicated the crucial regulator roles of a long non-coding RNA (lncRNA) LINC00673 in cancer pathogenesis and development. However, the clinical significance and functional effects of LINC00673 in cervical cancer remains unknown. METHODS: LINC00673 mRNA expression in cervical cancer tissues was measured by quantitative Real-time PCR (qRT-PCR), and the association between LINC00673 expression and the overall survival (OS) time of patients was analyzed by Kaplan-Meier survival plot. Cell proliferation was assessed using CCK8 assay, Flow cytometry analysis and cell colony formation assay. The association between miR-126-5p and LINC00673 was clarified by Luciferase activity assay. Furthermore, xenografts model in mice in vivo were used to evaluate the effects of LINC00673 expression on tumor growth of cervical cancer. RESULTS: It was confirmed that the relative mRNA expression of LINC00673 was promoted in cervical cancer tissues and cancer cell lines compared with its corresponding normal tissues and cells (P < 0.05). Higher LINC00673 expression was associated with tumor size, lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.05). Survival analysis showed higher LINC00673 expression predicted poor OS of cervical cancer patients, and Multivariate Cox analysis demonstrated that higher LINC00673 expression was identified as an independent risk factor for OS. LINC00673 overexpression promoted cell proliferation and cell cycle progression, but LINC00673 knockdown inhibited cell proliferation and cell cycle progression significantly (P < 0.05). Besides, overexpression of LINC00673 was negatively correlated with lower miR-126-5p expression in cervical cancer tissues. In vivo xenograft tumor assay indicated that LINC00673 silencing reduced the tumor volume and weight. Bioinformatics analysis revealed that miR-126-5p targeted 3'-UTR of LINC00673, and LINC00673 promoted cell proliferation by sponging to miR-126-5p in cervical cancer cells. Additionally, it was demonstrated that LINC00673 significantly activated the PTEN/PI3K/AKT signaling pathway in cervical cancer cells. CONCLUSION: These results provide the evidence that LINC00673 overexpression promotes cervical cancer cells progression through regulating miR-126-5p and activating the PTEN/PI3K/AKT signaling pathway, indicating that LINC00673 may be a potential therapeutic target for cervical cancer treatment.
BACKGROUND: Recent studies have indicated the crucial regulator roles of a long non-coding RNA (lncRNA) LINC00673 in cancer pathogenesis and development. However, the clinical significance and functional effects of LINC00673 in cervical cancer remains unknown. METHODS:LINC00673 mRNA expression in cervical cancer tissues was measured by quantitative Real-time PCR (qRT-PCR), and the association between LINC00673 expression and the overall survival (OS) time of patients was analyzed by Kaplan-Meier survival plot. Cell proliferation was assessed using CCK8 assay, Flow cytometry analysis and cell colony formation assay. The association between miR-126-5p and LINC00673 was clarified by Luciferase activity assay. Furthermore, xenografts model in mice in vivo were used to evaluate the effects of LINC00673 expression on tumor growth of cervical cancer. RESULTS: It was confirmed that the relative mRNA expression of LINC00673 was promoted in cervical cancer tissues and cancer cell lines compared with its corresponding normal tissues and cells (P < 0.05). Higher LINC00673 expression was associated with tumor size, lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.05). Survival analysis showed higher LINC00673 expression predicted poor OS of cervical cancerpatients, and Multivariate Cox analysis demonstrated that higher LINC00673 expression was identified as an independent risk factor for OS. LINC00673 overexpression promoted cell proliferation and cell cycle progression, but LINC00673 knockdown inhibited cell proliferation and cell cycle progression significantly (P < 0.05). Besides, overexpression of LINC00673 was negatively correlated with lower miR-126-5p expression in cervical cancer tissues. In vivo xenograft tumor assay indicated that LINC00673 silencing reduced the tumor volume and weight. Bioinformatics analysis revealed that miR-126-5p targeted 3'-UTR of LINC00673, and LINC00673 promoted cell proliferation by sponging to miR-126-5p in cervical cancer cells. Additionally, it was demonstrated that LINC00673 significantly activated the PTEN/PI3K/AKT signaling pathway in cervical cancer cells. CONCLUSION: These results provide the evidence that LINC00673 overexpression promotes cervical cancer cells progression through regulating miR-126-5p and activating the PTEN/PI3K/AKT signaling pathway, indicating that LINC00673 may be a potential therapeutic target for cervical cancer treatment.