ABSTRACT
HOTTIP RNA is a type of long non-coding RNA, which is transcribed from the HOXA gene at its distal tip and coordinates the activation of 5'HOXA genes. Particularly, it regulates the expression of the neighboring HOXA 13 gene. Recently, emerging lines of evi-dence have suggested that increased expression of HOTTIP is observed in digestive system carcinomas, including esophageal cancer, gastric cancer, hepatocellular carcinomas, pancreatic cancer, and colorectal cancer, and is closely associated with the initiation and pro-gression of cancer, and affects the survival and prognosis of cancer patients. Therefore, it is expected to be a diagnosis index marker, prognosis indicator, and a new therapeutic target for the relevant tumors. Here, we focus on the discovery of lncRNA HOTTIP, its mech-anism, and the latest developments in the research on HOTTIP in digestive system carcinomas.
ABSTRACT
Objective:The significant role of long non-coding RNAs (lncRNAs) in early diagnosis and predicting prognosis has been recognized in various cancers recently.However,the prognostic value of HOXA transcript at the distal tip (HOTTIP),a vital lncRNA in tumorigenesis,remains unclear.In this study,we evaluated its prognostic value by analyzing the correlation of HOTTIP expression with overall survival (OS),lymph node metastasis (LNM) and distant metastasis (DM) in different cancer types by meta-analysis.Methods:We performed a systematic search in PUBMED,MEDLINE,Web of Science and Cochrane Library update to November of 2016.A total of 604 patients from 6 studies were included in final analysis and went through a quantitative meta-analysis by Review manager 5.3.Results:We demonstrated that high expression of HOTTIP had a significant correlation with poor OS (hazard ratio [HR] =2.37,95％ confidence interval [CI] =1.81-3.10,p＜0.001),high LNM rate (odds ratio [OR]=2.29,95％CI=1.54-3.40,p＜0.001) as well as more DM occurrence (OR=3.30,95％CI=1.78-6.12,p＜0.001).Conclusion:Our results indicated that long non-coding RNA HOTTIP may serve as a potential prognostic biomarker in cancer progression.
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Background and purpose:Exploration of the effective early diagnostic and prognostic markers of non-small cell lung cancer (NSCLC) has important scientiifc signiifcance and clinical value. Recently, the role of long chain non-coding RNA (lncRNA) in the tumor attracts widespread attention. This study intended to investigate the level of lncRNA HOTTIP in NSCLC, the effect of HOTTIP on cell proliferation and its mechanisms.Methods:Expression of lncRNA HOTTIP in tumor and their matched non-tumor tissues were determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then, we analyzed the potential correlation of lncRNA HOTTIP expression levels in tumor tissues with clinicopathological features of NSCLC and clinical outcome. The effects of HOTTIP on NSCLC cell proliferation and apoptosis were tested usingin vitro MTT and lfow cytometric assays. Western blot method was uesd to detect the expressions of proteins.Results:LncRNA HOTTIP expression level was signiifcantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues (P<0.05). It was also proved that HOTTIP expression was associat-ed with NSCLC histological grade and lymph node metastasis. Moreover, knockdown of HOTTIP expression in A549 cell line decreased proliferation and enhanced apoptosis compared with transfected negative control. Western blot assay showed that the level of Bax protein was signiifcantly increased, whereas Bcl-2 was signiifcantly decreased in HOT-TIP-silencing A549 cell.Conclusion:HOTTIP is a novel prognostic biomarker and a potential therapeutic candidate forNSCLC.
ABSTRACT
Objective To investigate the potential biological effect of long non-coding RNA( lncRNA) HOXA transcript at the distal tip( HOTTIP) on proliferation, migration and invasion of cervical cancer cells.Methods HOTTIP small interference RNA(siRNA) was transfected into HeLa and C-33A cervical cancer cell lines, with negative siRNA as a control.qPCR assay was performed to confirm the knock-down of the level of HOTTIP.CCK8 assay and colony-forming unit (CFU) assay were performed to evaluate the effect of HOTTIP knock-down on HeLa and C-33A cell proliferation.Wound healing assay was performed to evaluate the effect of HOTTIP knock-down on HeLa and C-33A cell proliferation and migration.Tumor invasion assay was used to evaluate the effect of HOTTIP knock-down on HeLa and C-33A cell invasion. Results The expression level of HOTTIP was efficiently knocked down by siRNA 48 h post transfection.The results of CCK8 assay and CFU assay showed that HOTTIP knock-down significantly decrease of cervical cancer cell proliferation. Wound healing assay result indicated that HOTTIP knock-down obviously suppressed cervical cancer cell proliferation and migration.Tumor invasion assay results demonstrated that HOTTIP knock-down significantly suppressed cervical cancer cell invasion.Conclusion HOTTIP levels in HeLa and C-33A cervical cancer cell lines can be efficiently knocked down with the siRNA strategy, and the HOTTIP knock-down can significantly suppress the tumor characteristics of cervical cancer cells, including the ability of proliferation, migration and invasion.