Role of adenomatous polyposis coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives

Aghabozorgi, Amirsaeed Sabeti; Bahreyni, Amirhossein; Soleimani, Atena; Bahrami, Afsane; Khazaei, Majid; Ferns, Gordon A.; Avan, Amir; Hassanian, Seyed Mahdi

doi:10.1016/j.biochi.2018.11.003

Cited by 110 publications

(68 citation statements)

References 72 publications

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“…The progress of normal intestinal epithelial cell transition to unregulated cancer cell is a multi-stage and complicated process which is associated with the accumulation of both genetic and epigenetic changes. The aberration, mutations of oncogenes or tumor suppressive genes, and epigenetic alterations all lead to the progression of CRC [ 3 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

LINC02418 promotes colon cancer progression by suppressing apoptosis via interaction with miR-34b-5p/BCL2 axis

Tian

Cui

et al. 2020

Cancer Cell Int

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Background LncRNAs act as functional regulators in tumor progression through interacting with various signaling pathways in multiple types of cancer. However, the effect of LINC02418 on colorectal cancer (CRC) progression and the underling mechanisms remain unclear. Methods LncRNA expression profile in CRC tissues was investigated by the TCGA database. The expressional level of LINC02418 in CRC patients was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan–Meier analyses was used to investigate the correlation between LINC02418 and overall survival (OS) of CRC patients. Cell proliferative, migratory and invasive abilities were detected by CCK-8 assays, colony formation assays and trans-well assays in HCT116 and LoVo cells which were stably transduced with sh-LINC02418 or sh-NC. The binding between LINC02418 and miR-34b-5p, and the interaction between miR-34b-5p and BCL2 were determined by dual-luciferase assays. Western blot experiments were conducted to further explore the effect of miR-34b-5p on BCL2 signaling pathway. Rescue experiments were performed to uncover the role of LINC02418/miR-34b-5p/BCL2 axis in CRC progression. Results LINC02418 was upregulated in human colon cancer samples when compared with adjacent tissue, and its high expressional level correlated with poor prognosis of CRC patients. LINC02418 promoted cancer progression by enhancing tumor growth, cell mobility and invasiveness of colon cancer cells. Additionally, LINC02418 could physically bind to miR-34b-5p and subsequently affect BCL2 signaling pathway. Down-regulation of LINC02418 reduced cell proliferation, while transfection of miR-34b-5p inhibitor or BCL2 into LINC02418-silenced CRC cells significantly promoted CRC cells growth. Conclusions LINC02418 was upregulated in human CRC samples and could be used as the indicator for prediction of prognosis. LINC02418 acted as a tumor driver by negatively regulating cell apoptosis through LINC02418/miR-34b-5p/BCL2 axis in CRC.

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Section: Introductionmentioning

confidence: 99%

LINC02418 promotes colon cancer progression by suppressing apoptosis via interaction with miR-34b-5p/BCL2 axis

Tian

Cui

et al. 2020

Cancer Cell Int

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“…Embryonic mutations of the APC gene have been identified in familial adenomatous polyposis (FAP), a hereditary disease in which hun-dreds of colon polyps develop, leading to colon cancer. Somatic mutations in both APC alleles are also observed in more than 80% of sporadic, non-hereditary forms of colorectal cancer [5,20,21].…”

Section: Apc Genementioning

confidence: 99%

“…If an APC gene mutation occurs, the abnormal protein product lacks β-catenin binding capacity. Accumulated free β-catenin is continuously transported to the cell nucleus, activating genes responsible for cell division, increasing proliferation, and inhibiting differentiation [20,23].…”

Section: Apc Genementioning

confidence: 99%

Suppressor genes as molecular markers of colorectal cancer – a review of the latest reports

Piechowska¹,

Wawszczak²,

Cedro³

et al. 2020

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Suppressor gene research is one of the main current trends in modern cancer research. Oncogenesis, including colorectal cancer (CRC), is a process strictly dependent on the proper functioning of the suppressor genes and their proteins. The molecular genetic studies of hereditary cases and sporadic forms of cancer conducted for several years have revealed that a significant feature of the occurrence and progression of neoplastic changes is silencing of the expression of tissue-specific suppressor genes. Restoring the proper activity of the respective suppressor proteins plays a key role in anti-cancer prevention and gives hope for the development of effective personalised therapy. This review presents the latest reports on the molecular mechanisms regulating the expression, activity, and function of suppressor genes, which were silenced in tissues and cell lines of colorectal cancer, and restoration of their correct expression inhibited the proliferation and invasion of CRC cells. Streszczenie Badania genów supresorowych to jeden z głównych nurtów współczesnych badań nad nowotworami. Onkogeneza, również raka jelita grubego (CRC), jest procesem ściśle uzależnionym od właściwego działania genów supresorowych i kodowanych przez nie białek. Prowadzone od lat genetyczne badania molekularne przypadków dziedzicznych oraz postaci sporadycznych nowotworów wykazały, że znamienną cechą wystąpienia i progresji zmian nowotworowych jest wyciszenie ekspresji charakterystycznych dla danej tkanki genów supresorowych, a przywrócenie właściwej aktywności odpowiednich białek supresorowych odgrywa kluczową rolę w ochronie przeciwrakowej i daje nadzieję stworzenia skutecznej spersonalizowanej terapii antynowotworowej. W niniejszym opracowaniu przedstawiono najnowsze doniesienia na temat molekularnych mechanizmów regulujących ekspresję, aktywność i funkcję genów supresorowych, których wyciszenie zaobserwowano w tkankach i liniach komórkowych raka jelita grubego, a odtworzenie ich prawidłowej ekspresji hamowało proliferację oraz inwazję komórek CRC.

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“…Under normal conditions, the Apc protein interacts with β-catenin together with casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3) to form a destruction complex which renders β-catenin in an inactive state in the cytoplasm. Interestingly, mutations in the Apc gene were not exclusively found in FAP patients, but also in many sporadic colorectal tumors [ 11 , 12 ]. Besides the Wnt/β-catenin signaling pathway other signaling cascades critical for keeping the integrity of the intestine including the transforming growth factor β (TGFβ)-Smad signaling module, the phospho i nositide-3 (PI3)- and Akt kinases, the K-ras oncogene, or those driven by the tumor suppressor p53 are frequently altered in sporadic CRC [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma

Eberhardt

Haeussler

Nasrullah

et al. 2020

IJMS

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Colorectal cancer (CRC) is one of the most frequently diagnosed tumor in humans and one of the most common causes of cancer-related death worldwide. The pathogenesis of CRC follows a multistage process which together with somatic gene mutations is mainly attributed to the dysregulation of signaling pathways critically involved in the maintenance of homeostasis of epithelial integrity in the intestine. A growing number of studies has highlighted the critical impact of members of the tripartite motif (TRIM) protein family on most types of human malignancies including CRC. In accordance, abundant expression of many TRIM proteins has been observed in CRC tissues and is frequently correlating with poor survival of patients. Notably, some TRIM members can act as tumor suppressors depending on the context and the type of cancer which has been assessed. Mechanistically, most cancer-related TRIMs have a critical impact on cell cycle control, apoptosis, epithelial–mesenchymal transition (EMT), metastasis, and inflammation mainly through directly interfering with diverse oncogenic signaling pathways. In addition, some recent publications have emphasized the emerging role of some TRIM members to act as transcription factors and RNA-stabilizing factors thus adding a further level of complexity to the pleiotropic biological activities of TRIM proteins. The current review focuses on oncogenic signaling processes targeted by different TRIMs and their particular role in the development of CRC. A better understanding of the crosstalk of TRIMs with these signaling pathways relevant for CRC development is an important prerequisite for the validation of TRIM proteins as novel biomarkers and as potential targets of future therapies for CRC.

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Role of adenomatous polyposis coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives

Cited by 110 publications

References 72 publications

LINC02418 promotes colon cancer progression by suppressing apoptosis via interaction with miR-34b-5p/BCL2 axis

LINC02418 promotes colon cancer progression by suppressing apoptosis via interaction with miR-34b-5p/BCL2 axis

Suppressor genes as molecular markers of colorectal cancer – a review of the latest reports

Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma

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