• Journal of Microbiology and Biotechnology
• /
• 제31권7호
• /
• pp.921-932
• /
• 2021

LINC01272 is a long non-coding RNA (lncRNA) that has been considered as a biomarker for many diseases including lung squamous cell carcinoma. Here, we investigated the function and mechanism of LINC01272 on lung cancer (LC). The differential expression of LINC01272 in LC and normal samples was analyzed by GEPIA based on the data from TCGA-LUAD database, as survival prognosis was analyzed through Kaplan-Meier Plotter. LINC01272 overexpression plasmid and miR-7-5p mimic were transfected into A549 and PC-9 cells. LINC01272, miR-7-5p and cardiolipin synthase 1 (CRLS1) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction. Cell viability was detected through MTT assay. Cell multiplication was evaluated by cell formation assay. Cell apoptosis was assessed through flow cytometry assay. Through bioinformatics, the target miRNA of LINC01272 and downstream genes of miR-7-5p were predicted. The targeting relationship was tested by dual luciferase reporter analysis. CRLS1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax) and cleaved caspase-3 protein levels were detected through western blot. LINC01272 was downregulated in LC and low LINC01272 expression had poor prognosis. In A549 and PC-9 cells, LINC01272 inhibited cell viability and multiplication and induced apoptosis. LINC01272 negatively regulated miR-7-5p and CRLS1 was a target of miR-7-5p. MiR-7-5p reversed the effect of LINC01272 on viability, multiplication, apoptosis and expression of miR-7-5p and CRLS1 as well as apoptosis-related factors (Bcl-2, Bax and cleaved caspase-3). LINC01272 suppressed cell multiplication and induced apoptosis via regulating the miR-7-5p/CRLS1 axis in LC.

• Journal of Microbiology and Biotechnology
• /
• 제31권8호
• /
• pp.1098-1108
• /
• 2021

The literature indicates that LINC00174 promotes the growth of colorectal cancer (CRC) cells, but its research needs to be enriched. We tried to explore the function and mechanism of LINC00174 in CRC cell proliferation and migration. Bioinformatics analysis predicted the binding relationship and expressions of lncRNA, miRNA and mRNA. Clinical study analyzes the relationship between LINC00174 and clinical data characteristics of CRC patients. The expressions of LINC00174, miR-3127-5p and E2F7 were verified by RT-qPCR, and the combination of the two was verified by dual luciferase analysis and RNA immunoprecipitation as needed. Western blot was used to detect the expression of EMT-related protein and E2F7 protein. Functional experiments were used to evaluate the function of the target gene on CRC cells. LINC00174 was up-regulated in CRC clinical samples and cells and was related to the clinical characteristics of CRC patients. High-expression of LINC00174, contrary to the effect of siLINC00174, promoted cell viability, proliferation, migration and invasion, up-regulated the expressions of N-Cadherin, Vimentin, E2F7, and inhibited the expression of E-Cadherin. MiR-3127-5p was one of the targeted miRNAs of LINC00174 and was down-regulated in CRC samples. In addition, miR-3127-5p mimic partially reversed the malignant phenotype of CRC cells induced by LINC00174. Besides, E2F7 was a target gene of miR-3127-5p, and LINC00174 repressed miR-3127-5p to regulate E2F7. Our research reveals that LINC00174 affected the biological characteristics of CRC cells through regulated miR-3127-5p/ E2F7 axis.

• Journal of Microbiology and Biotechnology
• /
• 제31권10호
• /
• pp.1358-1365
• /
• 2021

To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.

• BLOOD RESEARCH
• /
• 제53권4호
• /
• pp.320-324
• /
• 2018

Background Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. Methods MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). Results MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. Conclusion Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

• 생명과학회지
• /
• 제31권6호
• /
• pp.568-573
• /
• 2021

본 연구는 전장 유전체 연관성 분석(genome-wide association study, GWAS)을 통해 ERp29의 mRNA 발현과 관련된 유전좌위(expression quantitative trait loci, eQTL)을 식별하는 것을 목표로 하였다. 대상 유전자는 ERp29이다. ERp29는 소포체(ER)의 lumen에 단백질의 folding & assembly 기능을 가진 분자 chaperone 단백질로서 소포체 스트레스에 의해 발현량이 증가하며, 분비 단백질의 생합성에 관여한다. 최근 연구 결과 발암과 연관성이 알려지면서 주목을 받고 있다. 총 373명의 유럽인의 genome을 대상으로 GWAS 분석 결과, ERp29 유전자 발현은 정소와 뇌에서 강하게 발현하는 long noncoding RNA (LncRNA) LOC105372577과 관계가 있었다. 즉, 3개의 eQTL: rs6138266 (p<4.172e10-9), rs62193420 (p<1.173e10-8), rs6138267 (p<2.041e10-8)와 연관성이 깊은 것으로 밝혀졌다. ERp29의 발현과 연관이 있는 것으로 확인된 3개의 eQTL을 사용한 transcriptome-wide association study (TWAS) 결과 osteosarcoma amplified 9 (OS9) 발현과 유의한 연관성을 보이며 OS9 유전자의 up-stream에 upstream of transcription factor 1 (USF1)이 결합할 수 있는 것을 알았다.

• BMB Reports
• /
• 제52권1호
• /
• pp.86-108
• /
• 2019

In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans.

• Molecules and Cells
• /
• 제45권6호
• /
• pp.388-402
• /
• 2022

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

• BMB Reports
• /
• 제56권3호
• /
• pp.184-189
• /
• 2023

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.