Abstract
Dear Sir,
The recent article on microRNA-221 (miR-221) in gastric cancer by Liu et al. 1 was highly interesting, as studies indicate that miR-221 may also be involved in the development and progression of other gastrointestinal tumors besides gastric carcinomas.
Increased expression of miR-221 is seen in nearly 88% of gastric carcinomas. It modulates phosphatase and tensin homolog expression and, thereby, increases proliferation in gastric tumors. 2 Not surprisingly, miR-221 helps in determining the prognosis in gastric malignancies. A poor clinical outcome and increased metastasis is seen in gastric tumors with upregulated miR-221 levels. 1 Not surprisingly, increased radiosensitivity as well as decreased proliferation are seen following miR-221 knockdown in gastric malignancies. 2
Similarly, pancreatic intraepithelial neoplastic lesions show accentuated expression of miR-221 and, interestingly, a study has indicated that miR-221 expression in pancreatic tumors can be downregulated by administration of the anticancer agent, benzyl isothiocyanate. 3 This may be how benzyl isothiocyanate attenuates tumor growth in aggressive pancreatic malignancies.
Accentuated miR-221 expression is seen in nearly 90% of colorectal carcinomas. Expression of cyclin-dependent kinase inhibitor 1C (CDKN1C; also known as p57 or Kip2) in colorectal carcinomas is decreased by miR-221. 4 An advanced tumor, node, metastasis (TNM) stage is generally seen with colorectal malignancies that express raised miR-221 levels. Not surprisingly, proliferation in colorectal carcinomas is markedly attenuated by anti-miR-221. 4
In breast tumors, miR-221 increases estrogen-independent proliferation by activating β-catenin. 5 Simultaneously, it increases cellular resistance to chemo -therapeutic agents such as fulvestrant. 5 In prostate carcinomas, more invasive tumors tend to express increased levels of miR-221 in addition to elevated miR-222 levels, compared with less invasive tumors. 6 Similarly, patients with malignant melanomas express accentuated serum levels of miR-221. Higher serum levels of miR-221 are associated with increased thickness in malignant melanomas and, thus, point towards a relatively poor clinical outcome. 7 The above examples clearly illustrate the role of miR-221 in the development of systemic malignancies, especially gastrointestinal malignancies, and the need for further research to identify inhibitors of miR-221 function.