MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.

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“…This cluster is induced by transcription factors c-myc and E2F3 159 . All six miRNAs are significantly overexpressed in colorectal tumors.…”

Section: Mir-17-92 Clustermentioning

confidence: 99%

Colorectal cancer carcinogenesis: a review of mechanisms

Tariq¹,

Ghias²

2016

Cancer Biology &Amp; Medicine

230

138

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“…No Rpa1 −/− mice were obtained, likely due to embryonic lethality. As azoxymethane (AOM) followed by three rounds of dextran sodium sulfate (DSS) [29] exposure produces a well-recognized model which mimics the genomic instability in human CRC [30][31][32], we generated an AOM/DSS-induced CRC model in Rpa1 +/− and Rpa1 +/+ mice in vivo as shown in Figure 5F. According to the AOM/DSS protocol ( Figure 5F), mice were euthanized and evaluated for cancer.…”

Section: Rpa1 Is Important For Suppression Of Colorectal Carcinomamentioning

confidence: 99%

PTEN regulates RPA1 and protects DNA replication forks

Wang

et al. 2015

Cell Res

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Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.

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“…Although it is known that epithelial dysplasia occurring in long-standing IBD is a typical precancerous lesion, the pathogenesis of colon cancer in IBD is poorly understood. Several studies have demonstrated the crucial role of altered miRNAs in the carcinogenesis of IBD-associated CRC (56,(81)(82)(83), which includes the detection of epigenetic regulation of miRNAs. By comparing the expression and promoter methylation status of miR-124a in tissue samples from UC patients with or without CRC, patients with sporadic CRC and healthy volunteers, Ueda et al observed significantly decreased expression and higher methylation levels of miR-124a in UC-associated CRC (56).…”

Section: Dna Methylation-mediated Regulation Of Mirnas In Crcmentioning

confidence: 99%

Reciprocal regulation between microRNAs and epigenetic machinery in colorectal cancer

Feng

Wang

et al. 2017

Oncology Letters

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Abstract. Epigenetics encompasses changes in DNA methylation, histone and chromatin structure, and non-coding RNAs, specifically microRNA (miRNA) expression. Recent advances in the rapidly evolving field of colorectal cancer (CRC) epigenetics have revealed a complicated network of reciprocal interconnections between miRNAs and other epigenetic machinery. On the one hand, miRNA expression may be regulated by epigenetic mechanisms including DNA methylation and histone modifications. However, miRNAs may affect the epigenetic machinery by directly targeting its enzymatic components. In this study, we focus on the colorectal miRNA expression profile and further illustrate the reciprocal regulation in CRC, with the aim of offering new insights into the strategies of combatting the disease.

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MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer

Cited by 256 publications

References 49 publications

Colorectal cancer carcinogenesis: a review of mechanisms

Colorectal cancer carcinogenesis: a review of mechanisms

PTEN regulates RPA1 and protects DNA replication forks

Reciprocal regulation between microRNAs and epigenetic machinery in colorectal cancer

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