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Table 8 potential chemoresistance genes proposed for further studies

From: Prediction of chemoresistance trait of cancer cell lines using machine learning algorithms and systems biology analysis

Potential chemoresistance genes Main role in cell
klhdc10 Except klhdc10, another client protein for kelch is phosphatase 5 (PP5) which in response to ROS inactivates ASK1. After this interaction, PP5 phosphatase activity will be suppressed. Furthermore, kelch mediates H2O2-induced sustained activation of ASK1 and cell death in Neuro2A cells
This data proposes that Slim/KLHDC10 is an activator for ASK1 and its activation through suppression of pp5 leads to oxidative stress-induced cell death [62]
MCRS1 Nucleolar MCRS1 which is called MSP58. It is proposed that TOJ3, an avian homologue of MSP58, is associated with Jun-induced cell transformation as well as tumorigenesis. Other studies have identified MSP58 as an oncogene hence its transformation activity was blocked by interaction with the PTEN tumor suppressor. It has also been reported that there exist different expression levels of MSP58 in human glioma and colorectal cancer [63]
MSH4 MSH4 mutation has been associated with lung cancer [64]. Furthermore, although hMSH4 and hMSH5 are not involved in DNA-mismatch correction but they participate in the Mutual recombination and appropriate separation of homologous chromosomes at meiosis [65]
nucb2 It has been proposed that NUCB2 is associated with metastasis in melanoma. Several studies have demonstrated that KLF4 levels are increased in melanoma cells leading to apoptosis inhibition and metastasis [66]
sh3gl2 It is proposed that SH3GL2 can have a tumor suppressor role in brain since deletion mutations in the locus of this gene can cause pilocytic astrocytomas. It has also been shown that through regulation of SH3GL2 gene, miR-330 affects proliferation, migration, invasion, cell cycle and apoptosis of human glioblastoma [67]
TMED5 malignant phenotypes including increased cell proliferation, EMT progression, apoptosis inhibition, cell migration and invasion, and drug resistance can emerge as a result of higher expression of TMED5 [68]. TMED5 is also proposed to play a role in NCI/ADR-RES drug-resistance (MDR) [69]
TMEM119 TMEM119 plays a role in migration and invasion of gastric cancer cells through activation of STAT3 signaling pathway which is found to be strongly correlated with the invasion, metastasis, and prognosis of gastric cancer [70]. Moreover, Zheng et al. showed that down-regulation of TMEM119 reduces Bcl-2 levels and increases Bax and caspase-3 levels in SGC-7901 cells [71]
TMEM219 The over-expression of TMEM219 gene which is localized in the membrane of breast, prostate, and pancreatic tumor cells, can suppress tumor growth. Other studies have revealed that expression levels of IGFBP 3 as well as its death receptor are in close relation to inefficient prognosis and low survival rate in pancreatic ductal adenocarcinoma [72]
WIPI1 WIPI1 up regulation has been detected in a variety of tumors. It has also been proposed that WIPI1 plays a role as an autophagy activator through TORC1 suppression. Furthermore, it has been stated that WIPI1 up regulation results in both lower relapses and higher survival rates in breast cancer [73]
YWHAH YWHAH gene can be considered as a potential target for therapeutic agents as it is down-regulated in
liposarcoma cells after Doxorubicin treatment [74]. Furthermore in another study, Kibel AS et al. proposed that YWHAH expression levels is positively correlated with malignant Prostate Cancer [75]
znf507 It has been proposed that over-expression of ZNF507 is associated with pancreatic, periampullary adenocarcinoma [76] as well as ovarian high-grade serous carcinomas (as an amplified ‘driver’ gene) [77]
ACP5 (TRAP-ACP5) can be used as a marker for predicting cancer progression and aggressiveness as it plays critical roles in many biologic processes such as bone resorption, osteoclast differentiation and, cell motility promotion through the modulation of focal adhesion kinase phosphorylation. It also acts as a metalloenzyme in activated osteoclasts and macrophages and also serves as a metastasis driver in cancer. It has been recently demonstrated that TRAP, through TGFβ2/TβR and CD44 signaling pathway, results in metastatic MDA-MB-231 breast cancer cells [78]
ANXA6 Several cancer types including Melanoma, CC, Epithelial Carcinoma, BC, GC, PCa, ALL, CML, large-cell lymphoma and myeloma have been proposed to be related to disregulation of AnxA6
Therefore, AnxA6 is a potential biomarker for identification, cure and prognosis of certain cancers [79]. Moreover, recent studies have proposed AnxA6 as a suggested target for inihibition of pancreatic cancer via antibodies [80]
Atp6v1g3 BSND and ATP6V1G3 has been proposed as novel immunohistochemical markers for the differential diagnosis of chromophobe RCC from other RCC subtypes and also diagnosis of chromophobe RCC metastasis to distant organs [81]
CWF19l2 CWF19 like cell cycle control factor 2 (PMID: 143,884). Breast cancer development has been related to ERBB2, MYC, GSTT1, PIK3CA and CWF19L2 [82]
DSC1 Dsc2 level is observed to decrease in colorectal cancer. The alterations in Dsc expression pattern can cause significant changes in desmosome function [83]. DSC1 can also be considered as a biomarker for tumor differentiation, and it can be a prognostic marker for lung cancer [84]
DUT DUT expression provides a discernible phenotype in a variety of cancers which can be used for prediction of patients response to chemotherapy as well as overall survival. It is significant to note that resistance to thymidylate synthase inhibitiors is related to 3–fivefold increased expression levels of dUTPase in HT29 and A549 cells [85]
EDNRB EDNRB methylation is helpful in screening of oral pre-malignancy and malignancy conditions [86]. hyper-methylation of the EDNRB gene has commonly occurred in NSCLC. Since the rate of EDNRB methylation is significantly higher in squamous cell carcinoma than adenocarcinomas, it can be used to distinguish SCCs from adenocarcinoma of the lung. since the downregulation of EDNRB after hypermethylation of the EDNRB gene is necessary for lung cancer tumorigenesis and is associated to tumor-related death [87]
FADS1 FADS1 rs174549 polymorphism is a useful factor for oral cancer PFS prediction, specifically in chemoradiotherapy patients. It can also be considered as a potential target for future of personalized treatment [88]
FAM65b FAM65B can be considered as a suitable target for therapeutic approaches based on cancer stem cell elimination. The reason is that overexpression of FAM65B is observed in Prostate tumors such as PC3. These tumors have stem like characteristics. For example, they are pro-angiogenic and strongly self-renewal [89]
FAM89b Fam89b is proposed to be a suitable target for chemotherapeutic strategies since it is a TGF-β pathway suppressor and signaling pathways induced by TGF-β have tumor-suppressing or tumor promoting effects based on type and stage of the cancer [90]
Gnai2 Previous studies have demonstrated GNAI2 as a main regulator of oncogenesis and an upstream driver of cancer development in the Ovarian cancer [91]. In addition to ovarian cancer, up-regulation of GNAI2 has also been observed in Hepatocellular Carcinoma. This protein acts through activation of the Ras-ERK/MAPK Mitogenic pathway by membrane recruitment of Rap1 GTPase-activating protein and moderation of GTP-bound Rap1 and also through the enhancement of cell survival by activation of AKT and inhibition of apoptosis by regulating Bcl-2 levels [92]