Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review

Pandurangan, Ashok Kumar; Divya, Thomas; Kumar, Kalaivani; Dineshbabu, Vadivel; Velavan, Bakthavatchalam; Sudhandiran, Ganapasam

doi:10.4251/wjgo.v10.i9.244

Cited by 72 publications

(36 citation statements)

References 157 publications

(149 reference statements)

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“…Activation of Smad3 is pivotal in the TGFβ/Smad pathway via the interaction of TGFβ and receptor. Phosphor-TGFβ receptor phosphorylates and initiates Smad2 and Smad3; therefore, the trimeric complex Smad2: Smad3: Smad4 establishes and triggered cell growth and survival (27). In the present study, we showed miR-145 reduced SMAD3 expression in vitro and in vivo, along with the decrease of Cdk4/Cyclin D1 and XIAP.…”

Section: Discussionsupporting

confidence: 59%

Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Fang

Wang

et al. 2020

Front. Oncol.

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An increasing number of studies have shown that long non-coding RNA (lncRNA) dysregulation plays a fundamental role in the development of various cancers, including colon cancer. Nonetheless, the mechanisms of lncRNA in regorafenib-resistance remain unclear. Our research revealed the lncRNA MIR570MG increased in regorafenib-resistant colon cancer cells compared to the regorafenib-sensitive cells. Furthermore, MIR570MG sponged miR-145, which declined in regorafenib-resistant colon cancer cell lines. More importantly, overexpression of miR-145 hampered cell proliferation and retrieved colon cancer regorafenib-sensitivity, contrary to the function of MIR570MG. Dual-luciferase reporter assay confirmed that miR-145 bound to 3 ′-UTR of SMAD3, a transcriptional modulator activated by TGFβ, resulting in blockage of TGFβ /SMAD3-mediated cell growth and cycle progression. Besides, ectopic expression of miR-145 inhibitor in the parental cells endowed resistance to regorafenib. Inversely, knockdown of MIR570MG impoverished resistance against regorafenib. Additionally, overexpression of MIR570MG conquered the suppression of tumor growth by miR-146 and rehabilitated the resistance to regorafenib in HCT116R human colon cancer mouse models. In summary, our findings suggested that MIR570MG promoted regorafenib resistance via releasing SMAD3 from miR-145, leading to activation of SMAD3-mediated signaling pathways.

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Section: Discussionsupporting

confidence: 59%

Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Fang

Wang

et al. 2020

Front. Oncol.

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“…Dysregulation in apoptosis pathways may include alteration of genes responsible in apoptosis modulation such as KRAS and TP53 . It has been reported that about 30% of CRC cases were linked to KRAS oncogene mutations [ 94 ] and about 70% were linked to the p53 mutations [ 95 , 96 , 97 ], where involvement includes cell survival, proliferation, and dysregulation of apoptosis [ 94 , 98 , 99 , 100 ]. In a normal colonic epithelium, a high number of apoptotic cells may be found at the top of the colon crypt.…”

Section: Discussionmentioning

confidence: 99%

The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells

et al. 2020

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The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.

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“…The genetic variation within genes encoding inflammatory mediators (6, 7) may have a modulatory role in colorectal carcinogenesis and affect the risk of developing CRC and survival. Due to different activated signaling cascades, the roles in later stages of cancer differ from those in early stages (3,15,(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer

et al. 2019

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Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients. Colorectal cancer (CRC) is one of the most common types of malignancy worldwide (1). The pathogenesis of CRC is still not fully understood and the molecular mechanisms underlying tumor progression and metastasis are unclear. Cancer-related inflammation appears to be a hallmark of CRC and cytokines play a central role in the carcinogenic process since they are key regulators of immune responses (2, 3). Several interleukins (ILs) modulate intestinal tumor development, differentiation, and inflammatory and antiinflammatory responses. IL2 secreted by T-helper type 1 (Th1) cells is an important factor in activating T-cellmediated immune responses and stimulating the proliferation and differentiation of B-cells and natural killer cells. In addition, IL2 is involved in development of regulatory Tcells (Tregs) (4, 5). Genetic variation, such as single nucleotide polymorphisms (SNPs), of inflammatory genes is suggested to play a role in the risk of CRC and survival of patients (6, 7). Polymorphic variants within the IL2/IL21 region at 4q27 have been discovered to be related to multiple diseases. The SNP rs6822844 is positioned in the IL2/IL21 intergenic region and is associated with multiple autoimmune diseases (8, 9). SNP rs11938795 is located in the same IL2/IL21 block and is related to Crohn's disease (10). Another SNP of the IL2 gene, rs2069762, is located in the promoter region and is implicated in increased susceptibility to gastric (11), oral (12), nasopharyngeal (13) and breast cancer (14). A hot topic in CRC research is the search for clinically applicable biomarkers that can aid in diagnosis, prognostication and prediction of treatment response (15, 16). CRC stag...

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Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review

Cited by 72 publications

References 157 publications

Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells

Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer

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