Table 2.
Effect of helicase depletion on cancer cell proliferation, tumour growth and sensitivity to chemotherapy or radiation
| Helicase | Growth or proliferation | Radiation or chemotherapy sensitivity |
|---|---|---|
| RECQL1 | RECQL1-targeted siRNA decreased proliferation, induced DNA damage and elevated SCE of endocervical carcinoma HeLa cells21, and induced mitotic cell death in lung, prostate, bladder, colon and liver cancer cells26 and HCC cells5 in vitro. RECQL1-targeted siRNA also suppressed tumour growth in mouse xenograft lung, liver, pancreatic and colorectal cancer models27, liver cancer with transplanted human HCC5, and nude mice carrying FaDu or D-562 hypopharyngeal carcinoma xenografts25. RECQL1-targeted siRNA decreased proliferation of human hypopharyngeal carcinoma25 and glioblastoma cells in vitro28. | RECQL1-targeted siRNA decreased proliferation of HeLa cells exposed to camptothecin or ionizing radiation21, and caused a camptothecin-induced replication restart defect in U2OS osteosarcoma cells in vitro129. RECQL1-targeted siRNA enhanced an antitumour effect of cisplatin in nude mice carrying FaDu hypopharyngeal carcinoma xenografts, and co-treatment with cisplatin increased DNA damage, apoptosis and mitotic catastrophe25. RECQL1-targeted siRNA and RECQL1-targeted shRNA sensitized glioblastoma28 and HeLa and U2OS cells24, respectively, to hydroxyurea in vitro. RECQL1-targeted siRNA sensitized glioblastoma cells to TMZ in vitro28. RECQL1-targeted shRNA sensitized HeLa and U2OS cells to 8-MOPS in vitro24. |
| WRN | WRN-targeted siRNA decreased proliferation of human hypopharyngeal carcinoma cells in vitro and suppressed tumour growth in nude mice carrying FaDu or D-562 hypopharyngeal carcinoma xenografts25. WRN-targeted shRNA decreased tumour establishment and tumour growth in MYC overexpressing non-small-cell lung cancer mouse xenografts184. | WRN-targeted siRNA enhanced the antitumour effect of cisplatin in nude mice carrying FaDu hypopharyngeal carcinoma xenografts; this combination increased DNA damage and induced apoptosis and mitotic catastrophe25. |
| BLM | BLM-targeted siRNA caused a 2.5-fold increase in SCE in HeLa cells 223. | NR |
| WRN and BLM | WRN-targeted shRNA or BLM-targeted shRNA decreased proliferation of U2OS cells in vitro with BLM depletion having a greater effect224. Cells co-depleted for WRN and BLM showed reduced proliferation that was comparable to BLM-depleted cells. | BLM-targeted or WRN-targeted shRNA sensitized U2OS cells to camptothecin, cisplatin or 5-FU. BLM-targeted shRNA sensitized U2OS cells to hydroxyurea. Co-depletion did not further sensitize cells to any tested chemotherapies224. |
| RECQL4 | RECQL4-targeted siRNA inhibited proliferation and increased DNA damage and apoptosis of prostate cancer cells in vitro. RECQL4-targeted shRNA caused metastatic cancer cells to display reduced cell invasiveness and suppressed tumour growth in nude mice7. | NR |
| RECQL5 | RECQL5-targeted shRNA decreased proliferation of HeLa cells in vitro29. | RECQL5-targeted shRNA increased 53BP1 foci in HeLa cells225. |
| FANCJ | FANCJ-targeted siRNA caused HeLa cells to display delayed G1/S progression and G1 accumulation132. | FANCJ-targeted siRNA decreased hydroxyurea-induced CHK1 phosphorylation in U2OS cells133 and proliferation of HeLa cells89 in vitro. FANCJ-targeted siRNA reduced the proliferation of MMC-exposed MCF7 breast cancer cells37 or HeLa cells89. FANCJ-targeted shRNA reduced the growth of MCF7 cells following exposure to ionizing radiation226. |
| DDX11 | DDX11-targeted siRNA caused mitotic failure and sister-chromatid cohesion defects in HeLa cells227,228; it also reduced proliferation and elevated chromosome segregation, telomere defects and apoptosis in melanoma cells229. | NR |
| PIF1 | PIF1-targeted siRNA reduced colony formation, increased sub-G1 DNA, and prolonged S phase in colon cancer cells (HCT116)55. | PIF1-targeted siRNA reduced survival and increased apoptosis of HCT116 cells exposed to thymidine, hydroxyurea or gemcitabine. Elevated apoptosis was observed in PIF1-depleted TP53−/− SW480 colon cancer and TP53+/+ MCF7 breast cancer cells55. |
| FBH1 | NR | FBH1-depleted U2OS cells exposed to hydroxyurea show reduced DSBs and apoptosis131. |
| RTEL | NR | RTEL-targeted siRNA decreased MMC resistance in HeLa cells49. |
5-FU, 5-fluorouracil; 8-MOPS, 8-methoxypsoralen; 53BP1, p53-binding protein 1; CHK1, checkpoint kinase 1; DSB, double-strand break; HCC, hepatocellular carcinoma; MMC, mitomycin C; NR, not reported; SCE, sister-chromatid exchange; shRNA, short hairpin RNA; siRNA, small interfering RNA; TMZ, temozolomide.