Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19

Abstract

HSPA5 (BiP, GRP78) has been reported as a potential host-cell receptor for SARS-Cov-2, but its expression profiles on different tissues including tumors, its susceptibility to SARS-Cov-2 virus and severity of its adverse effects on malignant patients are unclear. In the current study, HSPA5 has been found to be expressed ubiquitously in normal tissues and significantly increased in 14 of 31 types of cancer tissues. In lung cancer, mRNA levels of HSPA5 were 253-fold increase than that of ACE2 . Meanwhile, in both malignant tumors and matched normal samples across almost all cancer types, mRNA levels of HSPA5 were much higher than those of ACE2 . Higher expression of HSPA5 significantly decreased patient overall survival (OS) in 7 types of cancers. Moreover, systematic analyses found that 7.15% of 5,068 COVID-19 cases have malignant cancer coincidental situations, and the rate of severe events of COVID-19 patients with cancers present a higher trend than that for all COVID-19 patients, showing a significant difference (33.33% vs 16.09%, p <0.01). Collectively, these data imply that the tissues with high HSPA5 expression, not low ACE2 expression, are susceptible to be invaded by SARS-CoV-2. Taken together, this study not only indicates the clinical significance of HSPA5 in COVID-19 disease and cancers, but also provides potential clues for further medical treatments and managements of COVID-19 patients.

RNA-Sequencing Reveals Heat Shock 70-kDa Protein 6 (HSPA6) as a Novel Thymoquinone-Upregulated Gene That Inhibits Growth, Migration, and Invasion of Triple-Negative Breast Cancer Cells

“…Interestingly, recent studies found that TQ might have inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease ( 29 ), particularly for cancer patients ( 30 ). As we know, novel virus SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), and the World Health Organization (WHO) declared COVID-19 as a global pandemic as earlier of March 11, 2020 ( 31 – 33 ). As of the March 22, 2021, the total confirmed cases are 123,719,955, and death cases are 2,724,465 worldwide from the report of Johns Hopkins University ( ).…”

Current Understanding in the Pathophysiology of SARS-CoV-2-Associated Rhino-Orbito-Cerebral Mucormycosis: A Comprehensive Review

“…During SARS-CoV-2 infection, the viral spike glycoprotein triggers the endoplasmic reticulum stress [ERS] and stimulates the synthesis of GRP78 [ 51 ]. A prospective case control study reveals that the serum GRP78 was 5 times higher in COVID-19 as compared to the control group [ 52 , 53 ]. Furthermore, studies have demonstrated that the SARS-CoV-2 virus also uses the same GRP78 for its internalization into the host cells [ 51 ].…”

Heat Shock Protein Grp78/BiP/HspA5 Binds Directly to TDP-43 and Mitigates Toxicity Associated with Neurodegenerative Disease Pathology

“…TDP-43102-269 and TDP-431-102 were obtained as previously described 31,32 . The TDP-43 expression strain was described previously 37,38 . The Hsc70.3-WT or Hsc70.3 K97S Drosophila strains were obtained from the Bloomington Drosophila stock center, Indiana, USA.…”

“…HspA8 is well described for its implication in nuclear import of client proteins as it shuttles between the cytoplasm and nucleus 36 . Although HspA5 is mostly known for its ER localization, several studies have shown the presence of HspA5 in the nucleus 33,37,38 , including in SH-SY5Y cells 39 . Thus, our data suggest that in the SH-SY5Y cells and in the absence of stress, HspA5 and HspA8 selectively associate with nuclear but not cytoplasmic, TDP-43.…”