MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy

Cao, Zhe; Qiu, Jiangdong; Ye, Gang; Liu, Yueze; Luo, Wenhao; You, Lei; Zheng, Lianfang; Zhang, Taiping

doi:10.20892/j.issn.2095-3941.2020.0033

Cited by 31 publications

(27 citation statements)

References 112 publications

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“…In 1993, the discovery of microRNAs (miRNAs) improved our knowledge of biological mechanisms and their regulations in cells [ 100 – 103 ]. These short ncRNAs have a length of 22 nucleotides and can bind to complementary target messenger RNA (mRNA) via 3′-untranslated region (3′-UTR) [ 104 ].…”

Section: Non-coding Rnas and Ezh2 Signalingmentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

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Section: Non-coding Rnas and Ezh2 Signalingmentioning

confidence: 99%

The long and short non-coding RNAs modulating EZH2 signaling in cancer

et al. 2022

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“…Interestingly, these effects were suppressed by a miR-497 inhibitor, indicating that miR-497 and GACAT3 cooperate to induce EMT and to enhance cell invasion and migration ( Zhong et al, 2018 ). In glioma, GACAT3 substantially upregulates NAMPT expression, which enhances cell migration and invasion via sponging miR-135a in U87 and U251 cells ( Wang et al, 2019a ; Cao et al, 2020 ). Another study reported that silencing GACAT3 in U251 and A172 cells inhibited EMT by suppressing the levels of N-cadherin and elevating the levels of E-cadherin.…”

Section: Regulation Of Tumorigenesis and Progressionmentioning

confidence: 99%

“…The lncRNA gastric cancer-associated transcript 3 ( GACAT3 , also known as AC130710) is one such example of a cancer-associated lncRNA ( Li et al, 2020 ). GACAT3 functions as a competing endogenous RNA (ceRNA) and is encoded by human chromosome 2p24.3 ( Xia et al, 2014 ; Cao et al, 2020 ). Previous studies have shown that GACAT3 is involved in non-malignant diseases, including osteoarthritis ( Li et al, 2018a ).…”

Section: Introductionmentioning

confidence: 99%

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

Yuan

Dong

Shen

2022

Front. Cell Dev. Biol.

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Long non-coding RNAs (lncRNAs) are a class of functional RNA molecules that do not encode proteins and are composed of more than 200 nucleotides. LncRNAs play important roles in epigenetic and gene expression regulation. The oncogenic lncRNA GACAT3 was recently discovered to be dysregulated in many tumors. Aberrant expression of GACAT3 contributes to clinical characteristics and regulates multiple oncogenic processes. The association of GACAT3 with a variety of tumors makes it a promising biomarker for diagnosis, prognosis, and targeted therapy. In this review, we integrate the current understanding of the pathological features, biological functions, and molecular mechanisms of GACAT3 in cancer. Additionally, we provide insight into the utility of GACAT3 as an effective diagnostic and prognostic marker for specific tumors, which offers novel opportunities for targeted therapeutic intervention.

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“…The abnormal expression of miRNAs can affect the apoptosis, proliferation, and drug resistance in HCC[ 14 , 15 ]. In recent years, miR-135a has emerged as a critical miRNA in several cancers[ 16 ]. Several data suggest a markedly downregulated expression of miR-135a in some diseases and cancers[ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma

Wei¹,

Xia²,

Zhou³

et al. 2021

WJG

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BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The association of hepatitis B virus (HBV) infection with HCC is hitherto documented. Exosomal miRNAs contribute to cancer progression and chemoresistance. HBV X protein has been known to modulate miRNAs that facilitate cell proliferation and the process of hepatocarcinogenesis. However, there has been no report on hepatitis B core antigen (HBc) regulating exosomal miRNAs to induce drug resistance of HCC cells. AIM To elucidate the mechanism by which HBc promotes Doxorubicin hydrochloride (Dox) resistance in HCC. METHODS Exosomes were isolated by ultracentrifugation. The morphology and size of exosomes were evaluated by Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM). The miRNAs differentially expressed in HCC were identified using The Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissue samples was detected by quantitative polymerase chain reaction. TargetScan and luciferase assay were used to predict and prove the target gene of miR-135a-5p. Finally, we identified the effects of miR-135a-5p on anti-apoptosis and the proliferation of HCC in the presence or absence of Dox using flow cytometry, Cell counting kit 8 (CCK-8) assay and western blot. RESULTS We found that HBc increased the expression of exosomal miR-135a-5p. Integrated analysis of bioinformatics and patient samples found that miR-135a-5p was increased in HCC tissues in comparison with paracancerous tissues. Bioinformatic analysis and in vitro validation identified vesicle-associated membrane protein 2 (VAMP2) as a novel target gene of miR-135a-5p. Functional assays showed that exosomal miR-135a-5p induced apoptosis protection, cell proliferation, and chemotherapy resistance in HCC. In addition, the rescue experiment demonstrated that VAMP2 reversed apoptosis protection, cell growth, and drug resistance by miR-135a-5p. Finally, HBc promoted HCC anti-apoptosis, proliferation, and drug resistance and prevented Dox-induced apoptosis via the miR-135a-5p/VAMP2 axis. CONCLUSION These data suggested that HBc upregulated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2. Thus, our work indicated an essential role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC and a potential molecular therapeutic target for HCC.

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MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy

Cited by 31 publications

References 112 publications

The long and short non-coding RNAs modulating EZH2 signaling in cancer

The long and short non-coding RNAs modulating EZH2 signaling in cancer

LncRNA GACAT3: A Promising Biomarker and Therapeutic Target in Human Cancers

Hepatitis B core antigen modulates exosomal miR-135a to target vesicle-associated membrane protein 2 promoting chemoresistance in hepatocellular carcinoma

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