In silico analysis and experimental validation shows negative correlation between miR-1183 and cell cycle progression gene 1 expression in colorectal cancer.

MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by binding to the 3' untranslated regions (UTR) of target genes. Aberrant expression of miRNAs can lead to disease, including cancer. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Among several factors, differential expression of miRNA can have serious consequences on disease progression. This study was designed to computationally identify and experimentally verify strong miRNA candidates that could influence CRC progression. In silico analysis of publicly available gene expression microarray datasets revealed significant upregulation of miR-1183 in CRC. Comparison of mRNA microarray expression data with predicted miR-1183 targets led to the identification of cell cycle progression gene 1 (CCPG1) as strong, negatively correlated miR-1183 target. Expression analysis by means of quantitative PCR validated the inverse correlation between miR-1183 and CCPG1 in colorectal cancer tissues. CCPG1 indirectly modulates the cell cycle by interacting with the PH/DH domain of Dbs (Rho-specific guanine nucleotide exchange factor). Interestingly, the computational analysis also showed that miR-1183 is upregulated in liver and gastric cancer. This finding is notable as the liver and stomach are the primary metastatic sites for colorectal cancer and hepatocellular carcinoma respectively. This novel finding highlights the broader implications of miR-1183 dysregulation beyond primary CRC, potentially serving as a valuable prognostic marker and a therapeutic target for both primary and metastatic CRC.

Immunohistochemical Expression Of Cyclind1 In Conventional Squamous Cell Carcinomaof Oral Cavity.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, the incidence of which has significantly increased in the last 10 years. In Pakistan, it is reported to be the most common cancer among men and the second most common in women. Cyclin D1 is a protein involved in cell cycle regulation from G1 phase to S phase. Down regulation of this molecule causes inhibition of cell cycle transition and may lead to carcinogenesis. We studied the expression of Cyclin D1 in biopsies of oral squamous cell carcinoma to evaluate the staining patterns in various grades and sites of the oral cavity. Cyclin D1 was expressed in 53.8% cases of OSCC and showed a significant association with tumour differentiation, with higher intensity staining seen in poorly differentiated cases of OSCC. Thus, Cyclin D1 can be regarded as a marker of malignant potential of OSCC and can help identify cases with poorer outcome.

Neutrophil To Lymphocyte Ratio As A Predictor Of Severity In Colorectal Adenocarcinoma.

BACKGROUND: Colorectal cancers are slowly developing cancers of which more than 95% are adenocarcinomas, beginning in the mucus-producing glands lining the colon and rectum. In Pakistan, colorectal carcinoma is ranked as the seventh most common malignancy in men and the ninth most common in women with a male to female ratio of 9 to 1. This study aimed at investigating Neutrophil to Lymphocyte Ratio (NLR) as a potential marker for predicting severity of disease in terms of tumour histological grade in patients with pre-operative colorectal adenocarcinoma. METHODS: Retrospective cross-sectional study design was adopted and this study was conducted at the Department of Pathology, Pakistan Institute of Medical Sciences Islamabad. Sixty patients of all age-groups and both genders, diagnosed as colorectal adenocarcinoma on histopathological examination of resected specimens, were selected by consecutive non-probability sampling. Separately, 60 healthy subjects, age and sex-matched, were selected as control. RESULTS: Results revealed that the most common age group was 41-60 years showing 29 cases (48%) followed by the age group 61-80 years with 17 cases (28%). The most common site was the rectum having 24 cases (40%) followed by the right hemicolon with 13 cases (21.7%). The mean of neutrophil to lymphocyte ratio rose in direct proportion to the grade of colorectal carcinoma, showing a mean value of 4.5 in well differentiated low grade carcinoma, 5.0 in moderately differentiated and 6.0 in high grade poorly differentiated carcinoma. All patients had higher total leukocyte count, higher absolute neutrophil count, higher total neutrophil percentage and higher NLR as compared to their normal healthy counterparts. CONCLUSIONS: It is concluded that the NLR is directly proportional to tumour grade so it can be used preoperatively to assess whether the tumour is advanced so that it can be dealt with accordingly. This ratio can also be used as an independent screening marker for colorectal carcinoma since it shows very low levels in normal colonic epithelium.