The oncogene FOXM1 has been implicated in all major types of human cancer. We recently showed that aberrant FOXM1 expression causes stem cell compartment expansion resulting in the initiation of hyperplasia. We have previously shown that FOXM1 regulates HELLS, a SNF2/helicase involved in DNA methylation, implicating FOXM1 in epigenetic regulation. Here, we have demonstrated using primary normal human oral keratinocytes (NOK) that upregulation of FOXM1 suppressed the tumour suppressor gene p16INK4A (CDKN2A) through promoter hypermethylation. Knockdown of HELLS using siRNA re-activated the mRNA expression of p16INK4A and concomitant downregulation of two DNA methyltransferases DNMT1 and DNMT3B. The dose-dependent upregulation of endogenous FOXM1 (isoform B) expression during tumour progression across a panel of normal primary NOK strains (n = 8), dysplasias (n = 5) and head and neck squamous cell carcinoma (HNSCC) cell lines (n = 11) correlated positively with endogenous expressions of HELLS, BMI1, DNMT1 and DNMT3B and negatively with p16INK4A and involucrin. Bisulfite modification and methylation-specific promoter analysis using absolute quantitative PCR (MS-qPCR) showed that upregulation of FOXM1 significantly induced p16INK4A promoter hypermethylation (10-fold, P<0.05) in primary NOK cells. Using a non-bias genome-wide promoter methylation microarray profiling method, we revealed that aberrant FOXM1 expression in primary NOK induced a global hypomethylation pattern similar to that found in an HNSCC (SCC15) cell line. Following validation experiments using absolute qPCR, we have identified a set of differentially methylated genes, found to be inversely correlated with in vivo mRNA expression levels of clinical HNSCC tumour biopsy samples. This study provided the first evidence, using primary normal human cells and tumour tissues, that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a unique FOXM1-induced epigenetic signature which may have clinical translational potentials as biomarkers for early cancer screening, diagnostic and/or therapeutic interventions.

This study examines the nonlinear relationship between financial development and economic growth in Pakistan using the threshold regression model for the period 1980-2017. We also employed quantile regression with 0.25, 0.50, and 0.75 quantiles of conditional distribution. The quantile regression is based on minimizing of sum of squared residuals. The result indicates that economic growth responds positively to financial development when the level of financial development surpasses the threshold value of 0.151. However, when financial development lies below the threshold value (that is, 0.151), its impact on economic growth is negative. Thus, when financial development of Pakistan surpasses the threshold level, it contributes more towards economic growth since greater level of financial development contributes more to boosts economic growth. This finding reveals that economic growth reacts differently to financial development, and the relationship between financial development and economic growth is U-shaped in Pakistan. Among the other variables, physical capital, labor force, and government expenditure exert a positive effect on economic growth. Furthermore, inflation rate and trade openness have an insignificant impact on economic growth. The results of quantile regression also confirm the non-linear relationship between financial development and economic growth in Pakistan. The finding of this study suggests revamping of financial sector policies in Pakistan.

In this study, we examined the impact of principals' leadership style on the performance of teachers at the college level. For this purpose, we collect data from 300 college teachers via a random sampling approach. A self-administrated questionnaire (five-point Likert Scale) was used to collect data. For detecting relationships and differences among the opinions of the study's participants, correlation and the t-test were used. This study has revealed that the majority of college principals practice a democratic style of leadership at a higher level, Laissez-faire at a moderate level, and autocratic at a low level in their colleges. Moreover, it has been also revealed that when principals increase the use of a democratic leadership style, teacher performance may progress as well. The findings revealed that principals' leadership style had a positive impact on the performance of teachers. The study exposed a strong statistically positive relationship between college principals' leadership style and teacher performance. Thus, the results of this study suggest that college principals' should adopt the leadership style according to the level of teachers. The leadership style should be changed with specific situations in the colleges.

The focal purpose of this study is to analyze and explore the linkages of Pakistan Stock Exchange with the equity market of developing countries (Bangladesh, Singapore, Turkey, China and India) by applying co-integration approach to capture the short-run and longrun analysis. Monthly based secondary data containing stock indices of these equity markets covering the period from Jan 2015 to June 2019 has been used. Analysis of study shows that Pakistan Stock Exchange is not linked with the equity markets of Bangladesh and Singapore while it is correlated with the equity markets of China, Turkey and India. Results also show that PSX has short run relationship with developing countries like China, India and Turkey. No linkage with selected equity markets offers the investors and fund managers to get the better investment benefits in PSX. Existence of linkages of PSX-with the equity market reveals that the investors and fund managers of these countries do not have better investment opportunities in PSX. This study will help the investors in searching such equity markets which have greater investment benefits because linkages of equity market determines the better investment places. Investors and policy makers can make efficient investment decisions by studying these analyses. This study provides awareness and guideline to decision makers including local and foreign investors, agencies, financial analysts and banks about investment opportunities in equity market of Pakistan.