Upregulated, 7q21–22 amplicon candidate gene SHFM1 confers oncogenic advantage by suppressing p53 function in gastric cancer

Tamilzhalagan, Sembulingam; Muthuswami, Muthulakshmi; Periasamy, Jayaprakash; Lee, Ming Hui; Rha, Sun Young; Tan, Patrick; Ganesan, Kumaresan

doi:10.1016/j.cellsig.2015.02.010

Cited by 11 publications

(28 citation statements)

References 44 publications

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“…Elevated expression of MCM7 and COL1A2 are the features of intestinal and diffuse sub‐types of gastric cancer respectively . This was further confirmed in gastric cancer mRNA profile TCGA.…”

Section: Resultssupporting

confidence: 53%

“…The current results also reiterate the same. Earlier, SHFM1 set of genes were identified to involve in intestinal sub‐type gastric tumors with their contribution for oncogenesis also through c‐Src . The oncogenic protein c‐Src level was found marginally reduced upon silencing miR‐25‐3p in AGS cells (Fig.…”

Section: Resultsmentioning

confidence: 92%

“…Interestingly, these three miRNAs are the intronic miRNAs of MCM7 gene. MCM7 had earlier been identified to express in amplification driven manner in gastric tumors . Earlier reports also demonstrate the oncogenic role of MCM7 gene .…”

Section: Resultsmentioning

confidence: 92%

“…The recurrent genomic amplifications often possess oncogenic drivers. Earlier, the genomic amplification in 7q21.12‐22.3, which spans ∼20 Mb region was identified to have several potential oncogenes with amplification driven expression in gastric tumors and cell lines . Analysis of the miRNAs located in 7q21‐22 amplification would offer an easy opportunity for the identification of miRNAs that could target mRNAs and involve in carcinogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…It seems highly possible that miR‐25 and SHFM1 clusters of genes might synergistically function toward antagonizing the COL1A2 network of genes. Earlier, many of the SHFM1 cluster of genes were identified to involve in intestinal gastric cancers . The strong expression level association between SHFM1 and miR‐25 obviously indicates the involvement of miR‐25 in intestinal sub‐type of gastric tumors.…”

Section: Resultsmentioning

confidence: 99%

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Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

Tamilzhalagan

Rathinam

Ganesan

2017

Molecular Carcinogenesis

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Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7, and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 and MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors. Across gastric tumors, miR-25 was identified to co-express with MCM7 and SHFM1. On the other hand, negative correlation was observed between miR-25 and COL1A2 expression. miR-25 originating from MCM7 was found capable of selectively targeting the adjacent gene COL1A2. Silencing of miR-25 was found capable of elevating the expression of COL1A2 and inhibiting E-cadherin expression, revealing the diffuse type gastric cancer suppressive role conferred by miR-25. miR-25 was also found to suppress p53, and activate c-Src revealing its intestinal type gastric cancer associated oncogenic functions. Genome-wide expression profiling upon miR-25 silencing reveals that miR-25 is capable of suppressing 40 genes which are co-expressed with COL1A2, involved in epithelial to mesenchymal transition and angiogenesis which are the typical diffuse type gastric cancer features. The results clearly demonstrate 7q21-22 amplification, MCM7, and its intronic miR-25 are the major molecular switches involved in the complex oncogenic circuits of gastric cancer.

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

Tamilzhalagan

Rathinam

Ganesan

2017

Molecular Carcinogenesis

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Juxtaposed genes in 7q21‐22 amplicon contribute for two major gastric cancer sub‐Types by mutual exclusive expression

Tamilzhalagan

Muthuswami

Ganesan

2016

Molecular Carcinogenesis

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Genomic Copy Number Variations (CNV) and the associated gene signatures are useful for cancer prognosis, diagnosis, and targeted therapeutics. Earlier, 7q21-22 region was reported for frequent amplification in gastric cancer and potential candidate genes were identified. An analysis of the expression pattern of the 159 genes located in this amplicon revealed the consistent elevated expression of 21 genes in gastric tumors. These genes are closely arranged within the 20 Mb region, and they showed a bimodal expression pattern. SHFM1 and 14 other genes are expressed in intestinal type gastric tumors. COL1A2 and PCOLCE genes of this region are expressed in diffuse type gastric tumors. Similarly, genome-wide expression neighbors of SHFM1 and COL1A2 also showed mutually exclusive expression pattern, and stratify intestinal and diffuse type gastric tumors. The expression of COL1A2 gene-set is associated with poor prognosis, whereas the SHFM1 gene-set is associated with better prognosis among the gastric cancer patients. Despite being physical neighbors, the SHFM1 and COL1A2 genes express differentially in the two major clinical sub-types of gastric cancer in a mutually exclusive manner. The tight gene regulations operating between these juxtaposed genes deserve investigation to understand the molecular regulatory switch defining the determinants of the gastric cancer sub-types. © 2016 Wiley Periodicals, Inc.

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Proteasome dysregulation in human cancer: implications for clinical therapies

Chen

Zhang

Guo

2017

Cancer Metastasis Rev

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Cancer cells show heightened dependency on the proteasome for their survival, growth, and spread. Proteasome dysregulation is therefore commonly selected in favor of the development of many types of cancer. The vast abnormalities in a cancer cell, on top of the complexity of the proteasome itself, have enabled a plethora of mechanisms gearing the proteasome to the oncogenic process. Here, we use selected examples to highlight some general mechanisms underlying proteasome dysregulation in cancer, including copy number variations, transcriptional control, epigenetic regulation, and post-translational modifications. Research in this field has greatly advanced our understanding of proteasome regulation and will shed new light on proteasome-based combination therapies for cancer treatment.

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Upregulated, 7q21–22 amplicon candidate gene SHFM1 confers oncogenic advantage by suppressing p53 function in gastric cancer

Cited by 11 publications

References 44 publications

Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

Juxtaposed genes in 7q21‐22 amplicon contribute for two major gastric cancer sub‐Types by mutual exclusive expression

Proteasome dysregulation in human cancer: implications for clinical therapies

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