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Long non-coding RNA 00312 regulated by HOXA5 inhibits tumour proliferation and promotes apoptosis in Non-small cell lung cancer.

ABSTRACT: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer. The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported involved in the progression of various tumours, which can be used as diagnostic indicators or antitumour targets. Here, we found that the long non-coding RNA 00312 was down-regulated in paired NSCLC tissues and correlated with poor clinical outcome; decreased linc00312 expression in NSCLC was associated with larger and later stage tumours. Functional experiments showed that linc00312 could inhibit cell proliferation and promote apoptosis in vitro and in vivo. Furthermore, we found that HOXA5 could bind in the promoter of linc00312 and up-regulated the expression of it. Moreover, linc00312 was down-regulated in the plasma of NSCLC patients compared with that of healthy volunteers or other pulmonary diseases patients. Taken together, our findings indicated that linc00312 could be a novel diagnosis biomarker and a promising therapeutic target for NSCLC.

SUBMITTER: Zhu Q

PROVIDER: S-EPMC5571553 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Long non-coding RNA 00312 regulated by HOXA5 inhibits tumour proliferation and promotes apoptosis in Non-small cell lung cancer.

Zhu Qingqing Q Lv Tangfeng T Wu Ying Y Shi Xuefei X Liu Hongbing H Song Yong Y

Journal of cellular and molecular medicine 20170324 9

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer. The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported involved in the progression of various tumours, which can be used as diagnostic indicators or antitumour targets. Here, we found that the long non-coding RNA 00312 was down-regulated in paired NSCLC tissues and correlated with poor clinical outcome; decreased linc00312 expression in NSCLC was associated with larger and later stage tumours. ...[more]

PMID: 28338293

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Project description:BackgroundLong non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression.MethodsExpression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).ResultsMEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro.ConclusionsOur findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.

Project description:Endometrial carcinoma (EC) is the most common cancer in women worldwide, yet little is known about the underlying molecular basis of EC development. LINC01224, a novel long non‑coding (lnc)RNA, was recently identified as an oncogene in various types of cancer. However, the function and underlying mechanism of LINC01224 in EC is still unclear. A total of 50 pairs of tumor and adjacent normal tissue from patients with EC, three EC cell lines and one human normal endometrial stromal cell (ESC) line were subjected to reverse transcription‑quantitative PCR assay to evaluate the expression levels of LINC01224. Cell Counting Kit‑8, colony formation and flow cytometry assays were used to assess cell proliferation and apoptosis. Western blotting was used to measure expression levels of apoptosis‑ and proliferation‑associated proteins and AKT3 protein. A xenograft model of HEC1A cells was established to validate the in vivo function of LINC01224 in EC tumor growth. Starbase 3.0 database prediction and luciferase reporter and RNA pull‑down assays were performed to verify the binding sites between LINC01224 and microRNA (miR)‑485‑5p and miR‑485‑5p and AKT3. LINC01224 expression was significantly upregulated in both EC tumor tissue and cell lines. The upregulation of LINC01224 was negatively associated with survival of patients with EC. Functionally, LINC01224 promoted proliferation and inhibited apoptosis of EC cells; LINC01224 directly bound to and downregulated miR‑485‑5p to elevate the expression levels of AKT3, thereby promoting EC progression. LINC01224 depletion in EC cells hindered tumor growth in a xenograft model. The tumor suppressing effect of LINC01224‑knockdown on EC progression was partly rescued by treatment with miR‑485‑5p inhibitor. The present data demonstrated the expression levels, clinical relevance and functional mechanism of LINC01224 in EC. LINC01224 promoted EC development via sponging miR‑485‑5p to elevate AKT3 expression levels; this may provide a promising therapeutic target pathway for EC treatment.

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Long non-coding RNA 00312 regulated by HOXA5 inhibits tumour proliferation and promotes apoptosis in Non-small cell lung cancer.

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Long non-coding RNA 00312 regulated by HOXA5 inhibits tumour proliferation and promotes apoptosis in Non-small cell lung cancer.

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