Colorectal cancer (CRC) is one of the major causes of
cancer deaths across the world. Patients' survival at time of diagnosis depends mainly on stage of the
tumor. Therefore, understanding the molecular mechanisms from low-grade to high-grade stages of
cancer that lead to cellular migration from one tissue/organ to another tissue/organ is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary (primary sites), and metastatic samples (Colorectal metastatic lesions in liver and lung) in some Test datasets. DEGs were employed to construct a
protein-
protein interaction (PPI) network. A smaller network containing 39 DEGs was then extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit
tumor progression or
metastasis. These DEGs were then verified by gene expression profiling, survival analysis, and multiple Validation datasets. We suggested for the first time that downregulation of mitochondrial genes, including ETHE1, SQOR, TST, and GPX3, would help
colorectal cancer cells to produce more energy under hypoxic conditions through mechanisms that are different from "Warburg Effect". Augmentation of given
antioxidants and repression of P4HA1 and
COL1A2 genes could be a choice of CRC treatment. Moreover, promoting active GSK-3β together with expression control of
EIF2B would prevent EMT. We also proposed that OAS1 expression enhancement can induce the anti-
cancer effects of
interferon-gamma, while suppression of CTSH hinders formation of focal adhesions. ATF5 expression suppression sensitizes
cancer cells to anchorage-dependent death signals, while
LGALS4 induction recovers cell-cell junctions. These inhibitions and inductions would be another combinatory mechanism that inhibits EMT and cell migration. Furthermore, expression inhibition of
TMPO, TOP2A, RFC3, GINS1, and CKS2 genes could prevent
tumor growth. Besides, TRIB3 suppression would be a promising target for anti-angiogenic
therapy. SORD is a poorly studied
enzyme in
cancer, found to be upregulated in CRC. Finally, TMEM131 and DARS genes were identified in this study whose roles have never been interrogated in any kind of
cancer, neither as a
biomarker nor curative target. All the mentioned mechanisms must be further validated by experimental wet-lab techniques.