Limits...
High mobility group a proteins as tumor markers.

Pallante P, Sepe R, Puca F, Fusco A - Front Med (Lausanne) (2015)

Bottom Line: Almost 30 years ago, overexpression of HMGA proteins was associated with malignant phenotype of rat thyroid cells transformed with murine retroviruses.Here, we summarize all these results that, in the large majority of the cases, confirm the association of HMGA overexpression with high malignant phenotype as outlined by chemoresistance, spreading of metastases, and a global poor survival.In particular, the expression of HMGA2 in lung carcinomas is frequently associated with the presence of metastases.

View Article: PubMed Central - PubMed

Affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples , Italy.

ABSTRACT
Almost 30 years ago, overexpression of HMGA proteins was associated with malignant phenotype of rat thyroid cells transformed with murine retroviruses. Thereafter, several studies have analyzed HMGA expression in a wide range of human neoplasias. Here, we summarize all these results that, in the large majority of the cases, confirm the association of HMGA overexpression with high malignant phenotype as outlined by chemoresistance, spreading of metastases, and a global poor survival. Even though HMGA proteins' overexpression indicates a poor prognosis in almost all malignancies, their detection may be particularly useful in determining the prognosis of breast, lung, and colon carcinomas, suggesting for the treatment a more aggressive therapy. In particular, the expression of HMGA2 in lung carcinomas is frequently associated with the presence of metastases. Moreover, recent data revealed that often the cause for the high HMGA proteins levels detected in human malignancies is a deregulated expression of non-coding RNA. Therefore, the HMGA proteins represent tumor markers whose detection can be a valid tool for the diagnosis and prognosis of neoplastic diseases.

No MeSH data available.


Related in: MedlinePlus

The network of HMGA regulatory mechanisms in human carcinomas. (A) In breast carcinoma, HMGA1 is able to simultaneously repress the expression of CBX7 and induce the expression of miR-181b. This latter, together with CBX7, takes part to a reciprocal regulation. (B) HMGA2, overexpressed in lung carcinomas, acts as competing endogenous RNA for let-7, allowing the activation of the TGF-beta signaling through the upregulation of TGFBR3. Decreased expression of TTF-1 in lung carcinomas allows the overexpression of HMGA2 protein directly, by releasing the transcriptional block on its promoter, and indirectly, by removing the translational block due to miR-33b. HMGA1 is able to induce the expression of miR-222, which in turn can target p27kip1 and PPP2R2A, then activating the AKT signaling. (C) The loss of miR-34b expression in cancer cells allows the overexpression of HMGA1, which in turn alters the miR-34b pathway by repressing it and its inducer p53. (D) The presence of several let-7 binding sites in the 3′ untranslated regions of HMGA1, HMGA2, and relative pseudogenes (HMGA1P, HMGA2P) alters the epigenetic modulation of HMGA2 and HMGA1 themselves (respectively), allowing their overexpression after decoy of let-7 microRNA. Dashed rectangles/ovals and lines represent decreased expression or loss of regulatory action, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4373383&req=5

Figure 1: The network of HMGA regulatory mechanisms in human carcinomas. (A) In breast carcinoma, HMGA1 is able to simultaneously repress the expression of CBX7 and induce the expression of miR-181b. This latter, together with CBX7, takes part to a reciprocal regulation. (B) HMGA2, overexpressed in lung carcinomas, acts as competing endogenous RNA for let-7, allowing the activation of the TGF-beta signaling through the upregulation of TGFBR3. Decreased expression of TTF-1 in lung carcinomas allows the overexpression of HMGA2 protein directly, by releasing the transcriptional block on its promoter, and indirectly, by removing the translational block due to miR-33b. HMGA1 is able to induce the expression of miR-222, which in turn can target p27kip1 and PPP2R2A, then activating the AKT signaling. (C) The loss of miR-34b expression in cancer cells allows the overexpression of HMGA1, which in turn alters the miR-34b pathway by repressing it and its inducer p53. (D) The presence of several let-7 binding sites in the 3′ untranslated regions of HMGA1, HMGA2, and relative pseudogenes (HMGA1P, HMGA2P) alters the epigenetic modulation of HMGA2 and HMGA1 themselves (respectively), allowing their overexpression after decoy of let-7 microRNA. Dashed rectangles/ovals and lines represent decreased expression or loss of regulatory action, respectively.

Mentions: Interestingly, in breast carcinoma, HMGA1 takes part in an important regulatory circuitry involving CBX7 and miR-181b microRNA (miRNA) (34) (Figure 1A). HMGA1 enhances the expression of miR-181b, which in turn, represses the translation of CBX7 mRNA. The transcription of CBX7 is also directly repressed by HMGA1 itself (34) (Figure 1A).


High mobility group a proteins as tumor markers.

Pallante P, Sepe R, Puca F, Fusco A - Front Med (Lausanne) (2015)

The network of HMGA regulatory mechanisms in human carcinomas. (A) In breast carcinoma, HMGA1 is able to simultaneously repress the expression of CBX7 and induce the expression of miR-181b. This latter, together with CBX7, takes part to a reciprocal regulation. (B) HMGA2, overexpressed in lung carcinomas, acts as competing endogenous RNA for let-7, allowing the activation of the TGF-beta signaling through the upregulation of TGFBR3. Decreased expression of TTF-1 in lung carcinomas allows the overexpression of HMGA2 protein directly, by releasing the transcriptional block on its promoter, and indirectly, by removing the translational block due to miR-33b. HMGA1 is able to induce the expression of miR-222, which in turn can target p27kip1 and PPP2R2A, then activating the AKT signaling. (C) The loss of miR-34b expression in cancer cells allows the overexpression of HMGA1, which in turn alters the miR-34b pathway by repressing it and its inducer p53. (D) The presence of several let-7 binding sites in the 3′ untranslated regions of HMGA1, HMGA2, and relative pseudogenes (HMGA1P, HMGA2P) alters the epigenetic modulation of HMGA2 and HMGA1 themselves (respectively), allowing their overexpression after decoy of let-7 microRNA. Dashed rectangles/ovals and lines represent decreased expression or loss of regulatory action, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373383&req=5

Figure 1: The network of HMGA regulatory mechanisms in human carcinomas. (A) In breast carcinoma, HMGA1 is able to simultaneously repress the expression of CBX7 and induce the expression of miR-181b. This latter, together with CBX7, takes part to a reciprocal regulation. (B) HMGA2, overexpressed in lung carcinomas, acts as competing endogenous RNA for let-7, allowing the activation of the TGF-beta signaling through the upregulation of TGFBR3. Decreased expression of TTF-1 in lung carcinomas allows the overexpression of HMGA2 protein directly, by releasing the transcriptional block on its promoter, and indirectly, by removing the translational block due to miR-33b. HMGA1 is able to induce the expression of miR-222, which in turn can target p27kip1 and PPP2R2A, then activating the AKT signaling. (C) The loss of miR-34b expression in cancer cells allows the overexpression of HMGA1, which in turn alters the miR-34b pathway by repressing it and its inducer p53. (D) The presence of several let-7 binding sites in the 3′ untranslated regions of HMGA1, HMGA2, and relative pseudogenes (HMGA1P, HMGA2P) alters the epigenetic modulation of HMGA2 and HMGA1 themselves (respectively), allowing their overexpression after decoy of let-7 microRNA. Dashed rectangles/ovals and lines represent decreased expression or loss of regulatory action, respectively.
Mentions: Interestingly, in breast carcinoma, HMGA1 takes part in an important regulatory circuitry involving CBX7 and miR-181b microRNA (miRNA) (34) (Figure 1A). HMGA1 enhances the expression of miR-181b, which in turn, represses the translation of CBX7 mRNA. The transcription of CBX7 is also directly repressed by HMGA1 itself (34) (Figure 1A).

Bottom Line: Almost 30 years ago, overexpression of HMGA proteins was associated with malignant phenotype of rat thyroid cells transformed with murine retroviruses.Here, we summarize all these results that, in the large majority of the cases, confirm the association of HMGA overexpression with high malignant phenotype as outlined by chemoresistance, spreading of metastases, and a global poor survival.In particular, the expression of HMGA2 in lung carcinomas is frequently associated with the presence of metastases.

View Article: PubMed Central - PubMed

Affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples , Italy.

ABSTRACT
Almost 30 years ago, overexpression of HMGA proteins was associated with malignant phenotype of rat thyroid cells transformed with murine retroviruses. Thereafter, several studies have analyzed HMGA expression in a wide range of human neoplasias. Here, we summarize all these results that, in the large majority of the cases, confirm the association of HMGA overexpression with high malignant phenotype as outlined by chemoresistance, spreading of metastases, and a global poor survival. Even though HMGA proteins' overexpression indicates a poor prognosis in almost all malignancies, their detection may be particularly useful in determining the prognosis of breast, lung, and colon carcinomas, suggesting for the treatment a more aggressive therapy. In particular, the expression of HMGA2 in lung carcinomas is frequently associated with the presence of metastases. Moreover, recent data revealed that often the cause for the high HMGA proteins levels detected in human malignancies is a deregulated expression of non-coding RNA. Therefore, the HMGA proteins represent tumor markers whose detection can be a valid tool for the diagnosis and prognosis of neoplastic diseases.

No MeSH data available.


Related in: MedlinePlus