miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer

Xiao, Wang; Bu, Juyuan; Liu, Xingwei; Wang, Wenfeng; Mai, Weihua; Lv, Bao-Jun; Zou, Jian; Mo, Xiangqiong; Li, Xiaoling; Wang, Jingyu; Niu, Ben; Fan, Yunping; Hou, Bingzong

doi:10.18632/oncotarget.19212

Cited by 37 publications

(30 citation statements)

References 39 publications

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“…There are 12 genes, including HOXA1 to HOXA11 and HOXA13 ( 11 – 13 ). The HOXA gene cluster plays important roles in colorectal cancer, leukaemia, pancreatic cancer, oral squamous cell carcinoma and lung cancer ( 14 – 18 ). For HOXA3 , only one study suggests that it nat be used as a biomarker of LUAD.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Gan

Wei

et al. 2018

Int J Oncol

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Recent studies have indicated that homeobox A3 (HOXA3) functions as a carcinogen in colon cancer and the methylation level of HOXA3 is significantly increased in lung adenocarcinoma (LUAD) tissues. However, at least to the best of our knowledge, few studies to date have been performed on HOXA3 in non-small cell lung cancer (NSCLC). Therefore, further studies on HOXA3 expression in NSCLC and the potential regulatory mechanisms are urgently required. In this study, HOXA3 expression in 55 tissues of cases of NSCLC and corresponding non-lung cancer tissues was detected by reverse transcription-quantitative PCR (RT-qPCR). In addition, the clinical significance of HOXA3 expression in NSCLC was evaluated using the Cancer Genome Atlas (TCGA) database. Bioinformatics analysis was then performed to elucidate the potential molecular mechanisms of action of HOXA3. Furthermore, the potential target microRNAs (miRNAs or miRs) of HOXA3 were predicted using miRWalk2.0. Based on Gene Expression Omnibus (GEO) and TGCA databases, standardized mean difference (SMD) and sROC methods were used for meta-analyses of the expression of potential target miRNAs of HOXA3 in NSCLC to evaluate their association with HOXA3. The results revealed that the HOXA3 expression levels in NSCLC, LUAD and lung squamous cell carcinoma (LUSC) were 0.1130±0.1398, 0.1295±0.16890 and 0.0906±0.0846, respectively. These values were all decreased compared with the normal tissues (0.1877±0.1975, 0.2337±0.2405 and 0.1249±0.0873, respectively, P<0.05). The TCGA database also revealed the low expression trend of HOXA3. The downregulation of HOXA3 may play an important role in the progression and the poor prognosis of LUAD. The TCGA database also suggested that HOXA3 in LUAD and LUSC tissues exhibited certain mutational levels. In addition, the methylation levels in the NSCLC, LUAD and LUSC tissues significantly increased [NSCLC: fold change (FC), 1.3226; P<0.001; LUAD: FC, 1.2712; P<0.001; and LUSC: FC, 1.3786; P<0.001]. According to the analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the co-expression HOXA3 genes were mainly associated with the focal adhesion signalling pathway and the ECM-receptor interaction signalling pathway. Furthermore, the predicted miRNA, miR-372-3p, exhibited a high expression in both the NSCLC and LUAD tissues (P<0.05). On the whole, the findings of this study indicate that low HOXA3 expression may play a certain role in LUAD; however, its association with LUSC still requires further investigation. HOXA3 function may be achieved through different pathways or target miRNAs. However, the specific underlying mechanisms need to be confirmed through various functional studies.

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Section: Introductionmentioning

confidence: 99%

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Gan

Wei

et al. 2018

Int J Oncol

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“…Although it is recognized that miR-133b was usually down-regulated in various types of human cancer, such as bladder, prostate, gastric, colon cancer and gastrointestinal stromal tumor (GIST) [19][20][21][22][23], other tumor types showed an increased miR-133b which promotes cancer progression, such as hepatocellular carcinoma (HCC) and cervical carcinoma [24][25].…”

Section: Discussionmentioning

confidence: 99%

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor

et al. 2020

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Signaling pathways have a key role in driving the uncontrolled development of familial adenomatous polyposis (FAP)-associated and sporadic desmoid tumors (DTs). The relationship between the Wnt/b-catenin signaling pathway and DTs has been extensively studied, but no reliable biomarkers able to detect their histological subtype have been identified for the accurate diagnosis. In this study we studied the differences in miRNA expression between sporadic (20 patients) and FAP-associated DTs (7 patients) using microarray confirmed by quantitative PCR (qPCR). The analysis showed 19 dysregulated miRNAs. Among them miR-133b levels were significantly lower in FAP-associated DT than in sporadic DT. Therefore, two mRNAs, associated to miR-133b and β-catenin expression, the SIRT1 and ELAVL1were analyzed. The qPCR analysis showed that SIRT1 mRNA levels were significantly upregulated in FAP-associated DT than in sporadic DT, whereas no differences in ELAVL1 expression was observed between these two DT types. In addition, a negative correlation was observed between miR-133b and SIRT1 in FAP-associated DTs, but not in sporadic DTs. The miR-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated DT.

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“…miR-133b expression is significantly lower in colorectal cancer (CRC) samples or cell lines compared with normal controls. In addition, transfection with miR-133b can markedly hinder CRC cell proliferation and invasion in vitro and in vivo (26). The expression of miR-140-5p is reduced five-fold in breast cancer tissues compared with adjacent normal tissues, and is associated with advanced clinical procedure and poor prognosis (27).…”

Section: Discussionmentioning

confidence: 99%

miR-33a-5p enhances the sensitivity of lung adenocarcinoma cells to celastrol by regulating mTOR signaling

Sun

Hao

et al. 2018

Int J Oncol

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MicroRNAs (miRNAs or miRs) have recently become a popular focus of cancer research due to their ability to act as oncogenes or tumor suppressors. In the present study, miR‑33a‑5p expression was identified to be downregulated in lung adenocarcinoma samples compared with normal, which suggested that miR‑33a‑5p may serve as a tumor suppressor gene. Transfection with miR‑33a‑5p mimics inhibited the proliferation and migration of A549 and LTEP‑a‑2 cells and increased cellular apoptosis. A luciferase reporter assay confirmed that miR‑33a‑5p targets the 3'‑untranslated region of the mechanistic target of rapamycin (mTOR) gene. mTOR expression was decreased in A549 and LTEP‑a‑2 cells treated with miR‑33a‑5p mimics, as well as the expression of its downstream effectors phosphorylated (p)‑p70 ribosomal protein S6 kinase (p70S6K) and p‑eukaryotic translation initiation factor 4E binding protein 1 (4EBP1). Following treatment with celastrol, miR‑33a‑5p expression was upregulated, and miR‑33a‑5p could enhance cellular sensitivity to celastrol. Western blot analysis revealed that the expression of mTOR, p‑p70S6K and p‑4EBP1 decreased following celastrol treatment. These results suggested that mTOR was involved in the mechanism by which miR‑33a‑5p enhanced the sensitivity of lung adenocarcinoma cells to celastrol. Furthermore, LTEP‑a‑2 cells were xenografted subcutaneously into nude mice, to examine the effect of celastrol and miR‑33a‑5p on the growth of LTEP‑a‑2 cells in vivo. The results demonstrated that tumor growth in the celastrol‑treated or miR‑33a‑5p‑treated group was attenuated compared with the control group. Notably, tumor growth in the combination treatment group was almost arrested after 2 weeks. In addition, celastrol upregulated the expression of miR‑33a‑5p, and high expression of miR‑33a‑5p inhibited mTOR and its downstream effectors. In summary, miR‑33a‑5p inhibited the proliferation of lung adenocarcinoma cells, enhanced the antitumor effect of celastrol, and improved sensitivity to celastrol by targeting mTOR in lung adenocarcinoma in vitro and in vivo.

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miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer

Cited by 37 publications

References 39 publications

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor

miR-33a-5p enhances the sensitivity of lung adenocarcinoma cells to celastrol by regulating mTOR signaling

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