Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells

Ng, Lui; Li, Xue; Wan, Timothy Ming‐Hun; Iyer, Deepak Narayanan; Sin, Ryan Wai-Yan; Lo, Oswens Siu-Hung; Foo, Chi Chung; Law, Wai‐Lun

doi:10.1016/j.ejso.2021.09.016

Cited by 5 publications

(6 citation statements)

References 29 publications

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“…In the current investigation, tissue levels of MiR-663b gene expression were shown to be dysregulated in individuals with colorectal polyposis illness compared to levels calculated for healthy colorectal tissues. This data suggests a potential function for microRNA in the etiology of colorectal polyps and is consistent with earlier research indicating such a connection (16)(17)(18)(19) .…”

Section: Discussionsupporting

confidence: 92%

Role of MicroRNA-663b as an Oncogene in Colorectal Carcinoma on top of familial adenomatous polyposis cells.

T.mohamed

Hafez

A.Idris

et al. 2022

Benha Medical Journal

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Background: Familial polyposis coli (FPC) is almost always benign lesions presenting by bleeding or discovered accidentally during routine colonoscopy. However, malignant transformation could not be excluded and this necessitates early detection in the metaplasia stage. Aim: Evaluation of the ability of estimated tissue expression levels of microRNA-663b (MiR-663b) to distinguish benign from malignant rectal polyps in patients with FPC. Subjects & Methods: Forty-one patients with FPC were assessed clinically, had colonoscopic biopsies, and provided blood samples for estimation of serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 estimate (CA19-9). Tissue samples were separated into two portions, for pathological analysis and PCR analysis to determine the degree of MiR-663b expression in the tissue. Subjects undergoing colonoscopy for other reasons were subjected to a rectal biopsy.Results: The serum levels of CA 19-9 were considerably greater in MRP patients compared to healthy controls. The estimated tissue level of MiR-663b in three benign specimens was greater than the 4th quartile level of control specimens and in the range between the 1st and 2nd quartile levels of malignant specimens; these specimens were thus classified pre-malignant. A multivariate Regression analysis identified elevated miRNA366b gene expression as an independent risk factor for BRP malignant transformation.Conclusion:MiR-663b tissue expression estimation might be utilized to distinguish benign from malignant colorectal polyps. Whenever MiR-663b levels were greater than control levels but below than the levels diagnostic of malignancy, are able to predict the early malignant transformation of benign polyps prior to their being identified by pathology.

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Section: Discussionsupporting

confidence: 92%

Role of MicroRNA-663b as an Oncogene in Colorectal Carcinoma on top of familial adenomatous polyposis cells.

T.mohamed

Hafez

A.Idris

et al. 2022

Benha Medical Journal

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“…To validate our previous miRNA microarray results, which demonstrated that miR-187-3p was repressed in colorectal polyp and CRC tissues [ 17 ], DNA-primer-based reverse transcription PCR (RT-PCR) was performed to determine the expression of miR-187-3p in synchronous polyp, CRC, and normal mucosa samples from 14 patients. As shown in Figure 1 , miR-187-3p was significantly repressed in polyp ( p = 0.017) and CRC ( p = 0.009) tissues when compared to adjacent normal tissue, whereas no significant difference was observed between polyp and CRC tissues.…”

Section: Resultsmentioning

confidence: 99%

“…A DNA-primer-based reverse transcription PCR (RT-PCR) method was applied to determine the miR-187-3p levels, as previously described [ 17 ]. For RT-PCR, the total RNA was polyadenylated (New England Biolabs, Ipswich, MA, USA), and was subsequently reverse-transcribed using the PrimeScript RT Reagent Kit (Takara, Shiga, Japan) with a custom oligo dT primer.…”

Section: Methodsmentioning

confidence: 99%

“…These findings suggest heterogeneous roles of miR-187-3p in promoting or suppressing carcinogenesis among different cancer types. We previously identified the dysregulated expression of 39 miRNAs during the transformation process of colorectal cells, with miR-187-3p being one of the most repressed miRNAs in both colorectal polyp and CRC in comparison with adjacent normal tissue, suggesting its repression to be an early event in colorectal cells’ transformation [ 17 ]. Indeed, miR-187-3p has been shown to be downregulated in CRC, and to functionally regulate tumor cells’ proliferative and invasive behavior.…”

Section: Introductionmentioning

confidence: 99%

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High Levels of Tumor miR-187-3p—A Potential Tumor-Suppressor microRNA—Are Correlated with Poor Prognosis in Colorectal Cancer

Wan

Iyer

et al. 2022

Cells

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Background: The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis among CRC patients. This study further investigated the clinicopathological significance of miR-187-3p in CRC. Methods: MiR-187-3p levels in paired polyp/CRC/normal specimens or primary CRC/liver metastasis specimens were determined by qPCR, and correlated with the patient’s clinicopathological and postoperative survival data. The clinical findings were validated using our validation cohort and data obtained from the TCGA or GEO databases. The functional effects of miR-187-3p were investigated through its overexpression in CRC cell lines. Results: MiR-187-3p was significantly repressed in colorectal polyps and CRC when compared to adjacent normal tissue. Overexpression of miR-187-3p in CRC cell lines impaired colony formation, cell migration, and invasion, and induced chemosensitivity. Clinical analysis revealed that despite miR-187-3p being repressed in CRC, high tumor miR-187-3p levels were positively correlated with tumor stage and disease recurrence. Further analysis showed that miR-187-3p levels were lower in metastatic specimens when compared to paired primary CRC, suggesting that high tumor miR-187-3p levels resulted from the dissemination of metastatic tumor cells. Tumor miR-187-3p levels were positively correlated with peripheral inflammation-related blood markers. Finally, SPRY1 was identified as a novel target gene of miR-187-3p, and was involved in miR-187-3p-impaired CRC metastasis. Conclusions: This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers.

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“…MiR-192-3p has been reported to be dysregulated and significantly associated with survival in CRC. 36,37 In prostate cancer, miR-3167 has been proven to function as an anti-oncogene by regulating YWHAZ. 38 Moreover, we validated that miR-3167 exhibited a higher binding ability with circVMP1 than miR-192-3p and miR-3167 could bind with HKDC1.…”

Section: Discussionmentioning

confidence: 99%

CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer

Chen,

Li,

Yang

et al. 2023

Environmental Toxicology

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BackgroundCircular RNAs (circRNAs) have been reported to play important roles in cancers. Here, we characterized circVMP1 (hsa_circ_0006508), an important circRNA which promoted glycolysis and disease progression in colorectal cancer (CRC). In this study, we aimed to explore the mechanism by which circVMP1 regulated tumor glycolysis and its related pathways in promoting CRC cell proliferation and metastasis.MethodsThe expression level of circVMP1 in CRC tissues and adjacent normal tissues was detected using quantitative PCR. In vitro and in vivo functional experiments were used to evaluate the effects of circVMP1 in the regulation of CRC cell proliferation and migration. Mitochondrial stress tests and glycolysis stress tests were conducted to detect the effect of circVMP1 on oxidative phosphorylation and glycolysis. Dual‐luciferase reporter and RNA immunoprecipitation assays were used to evaluate the interaction between circVMP1, miR‐3167, and HKDC1.ResultsWe demonstrated that the level of circVMP1 was significantly upregulated in CRC tissues compared with normal tissues. In HCT116 and SW480 cells, overexpression of circVMP1 promoted proliferation, metastasis, and glycolysis. In vivo analysis indicated that circVMP1 accelerated the proliferation of xenograft tumors. As for the mechanism, overexpression of circVMP1 increased the levels of hexokinase domain component 1 (HKDC1) through competitive binding with miR‐3167.ConclusionOur study reported that circVMP1 was one of the tumor driver genes that promoted CRC malignant progression and glycolysis by upregulating HKDC1. CircVMP1/miR‐3167/HKDC1 was a signaling axis that might be a target for CRC therapy.

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Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells

Cited by 5 publications

References 29 publications

Role of MicroRNA-663b as an Oncogene in Colorectal Carcinoma on top of familial adenomatous polyposis cells.

Role of MicroRNA-663b as an Oncogene in Colorectal Carcinoma on top of familial adenomatous polyposis cells.

High Levels of Tumor miR-187-3p—A Potential Tumor-Suppressor microRNA—Are Correlated with Poor Prognosis in Colorectal Cancer

CircVMP1 promotes glycolysis and disease progression by upregulating HKDC1 in colorectal cancer

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